D Wong

Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy : Results from a randomized, double-blind, controlled clinical trial.

PURPOSEnTo assess the safety and efficacy of adjuvant combination therapy using 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) for prevention of proliferative vitreoretinopathy (PVR) after vitrectomy and retinal reattachment surgery.nnnDESIGNnProspective randomized, double-masked, placebo controlled trial.nnnPARTICIPANTSnOne hundred seventy-four high-risk patients were randomized to receive either 5-FU and LMWH therapy or placebo. Patients were selected from all patients undergoing primary vitrectomy for rhegmatogenous retinal detachment.nnnMETHODnResults of standard surgery with 5-FU and LMWH therapy or placebo were compared at the 6-month follow-up.nnnMAIN OUTCOME MEASURESnDevelopment of postoperative PVR, retinal reattachment at 6 months after surgery, single operation reattachment rate, number of reoperations, and best-corrected visual acuity.nnnRESULTSnThere were 87 patients in the 5-FU and LMWH therapy group and 87 in the placebo group. The incidence of postoperative PVR was significantly lower (P = 0.02) in the 5-FU and LMWH therapy compared with the placebo group. In 26.4% (23/87) of the placebo group and in 12.6% (11/87) of the 5-FU and LMWH group, postoperative PVR developed. In the 5-FU and LMWH group, the number of patients undergoing more than one operation was 19.5% (17/87) and the number of reoperations resulting from PVR was 52.9% (9/17). In the placebo group, the number of patients undergoing more than one operation was 25.3% (22/87) and the number of reoperations resulting from PVR was 72.7% (16/22). The difference in visual acuity was not statistically different in the two treatment groups, although those patients in whom postoperative PVR developed tended to have poorer vision (P < 0.0001). There were no differences in complication rates between the two groups.nnnCONCLUSIONSnThere is a significant reduction in the incidence of postoperative PVR in patients receiving the 5-FU and LMWH therapy and in the reoperation rate resulting from PVR. This trial shows that incidence of PVR can be reduced with inexpensive and simple pharmacologic treatment with 5-FU and LMWH and should be used routinely in the treatment of patients at risk of developing PVR.

Trypan blue staining of internal limiting membrane and epiretinal membrane during vitrectomy: visual results and histopathological findings.

Aims: To report on the use of trypan blue (TB) 0.06% for staining the internal limiting membrane (ILM) and epiretinal membrane (ERM) during vitrectomy and report on their histology. Method: 14 consecutive patients with idiopathic macular hole or macular pucker (seven patients each) were prospectively recruited for ILM or ERM peel respectively. After pars plana vitrectomy and induction of posterior vitreous detachment, 0.5 ml TB 0.06% in phosphate buffered saline (VisonBlue) was injected over the posterior pole in an air filled eye and left for 2 minutes. The stained tissue was peeled with intraocular forceps. Specimens were evaluated using histochemical and immunohistochemical methods. Results: The average follow up was 4.4 months. Internal limiting membranes and epiretinal membranes were stained satisfactorily in all cases and removed successfully. Eight patients (57%) had improvement of 2 or more Snellen lines. All seven macular holes closed. In the ERM cases, no residual membranes were observed clinically, at the latest follow up. No complications relating to the use of the dye were encountered intraoperatively or postoperatively. Of the 14 procedures, nine (four macular hole and five macular pucker) yielded sufficient tissue for histopathological evaluation. Histological and immunohistological assessment revealed that the morphology of these specimens was similar to that observed in macular hole ILM and macular pucker ERM removed without the aid of dye. Conclusion: TB staining facilitated the identification and delineation of ILM and ERM removal during the surgical management of macular holes and macular pucker. The visual outcome of this series and the specimens removed suggest they are no different from those without TB staining. Its use in posterior segment appears to be safe but further studies are required to investigate its long term safety.

Trypan blue staining in vitreoretinal surgery

PURPOSEnTo evaluate the efficacy of trypan blue for staining the internal limiting membrane (ILM) and epiretinal membranes (ERM) in vitreoretinal surgery.nnnDESIGNnProspective noncomparative case series.nnnPARTICIPANTSnFifty eyes of 50 patients with macular pucker (n = 22), macular hole (n = 18), or a combination (n = 2), proliferative vitreoretinopathy (n = 5), or diabetic retinopathy (n = 3).nnnMETHODSnTrypan blue 0.2% was used to stain the ILM or ERM during vitreoretinal surgery.nnnMAIN OUTCOME MEASURESnThe intraoperative visibility of the membranes was scored as poor, moderate, good, or excellent.nnnRESULTSnThe application of trypan blue onto the ILM or the ERM resulted in a useful bluish staining, facilitating the identification, delineation, and removal of the membranes in all surgeries. No residual staining or adverse effects related to the dye were observed.nnnCONCLUSIONSnTrypan blue stains both ILM and ERM and might be an useful tool in vitreoretinal surgery.

Heavy tamponade 1: a review of indications, use, and complications

BackgroundHeavier than water intraocular tamponades have several theoretical advantages over conventional tamponades, especially in the treatment of complicated retinal detachments and proliferative viteroretinopathy of the lower fundus periphery. However, initial clinical series of various heavy tamponades have reported significant complication rates. Therefore, heavy tamponades have not found widespread acceptance. Three recently developed heavy silicone oil tamponades, Oxane HD, Densiron 68, and HWS 46-3000, are much better tolerated and presently seem to enter routine clinical practice.Materials and methodsLiterature review of 21 publications on the clinical application of 9 different heavy tamponades (fluorosilicone, C10F18, F6H8, OL62HV, Oxane HD, O62, F6H8-silicone oil mixture, Densiron 68, and HWS 46-3000).ResultsThe first generation (fluorinated silicone and perfluorocarbon liquids) and second generation (partially fluorinated alkanes) of heavy tamponades were associated with relatively high complication rates, for example, tamponade emulsification, intraocular inflammation, and rise in intraocular pressure. The complication spectrum of the new generation of heavy silicone oils (Oxane HD, Densiron 68, and HWS 46-3000) seems to be comparable to conventional silicone oil tamponades while providing better support for the inferior retina and the posterior pole.ConclusionThe recently developed heavy silicone oil tamponades are safe and effective tools for the use of complicated retinal detachments of the inferior fundus.

How to predict proliferative vitreoretinopathy: a prospective study.

PURPOSEnTo determine prospectively the accuracy of a predictive risk formula for the development of postoperative proliferative vitreoretinopathy (PVR) when applied in a clinical setting.nnnDESIGNnProspective noncomparative interventional case series.nnnPARTICIPANTSnTwo hundred nineteen subjects undergoing primary vitrectomy for rhegmatogenous retinal detachment were studied.nnnMETHODnBy use of a formula-based discriminant rule, subjects were classified as either high or low risk for the development of PVR. All subjects were followed prospectively.nnnOUTCOME MEASURESnDevelopment of postoperative PVR as defined by the updated the Retina Society Classification.nnnRESULTSnComplete data were available on 212 of 219 subjects. There were 130 subjects identified as low risk and 82 subjects as high risk; 9.2% of the low-risk (12 of 130) compared with 28% (23 of 82) of the high-risk subjects had postoperative PVR develop. This difference was statistically significant (P < 0.001).nnnCONCLUSIONSnOur study has shown that using a clinical model it is possible to identify subjects at greater risk of PVR developing after primary vitrectomy.

Clinicopathological correlation of epiretinal membranes and posterior lens opacification following perfluorohexyloctane tamponade

BACKGROUND/AIMS Epiretinal and retrolental proliferation may occur during prolonged use of the novel tamponade agent perfluorohexyloctane (F6H8). This study aims to determine whether there is any histological evidence that F6H8has a role in the formation of these membranes. METHODS Eight epiretinal membranes and three opaque posterior lens capsules were excised from patients in whom F6H8 had been used as a long term retinal tamponade agent. The membranes and capsules were examined employing light microscopic methods, including immunohistochemistry. RESULTS The epiretinal membranes showed histological features typical of proliferative vitreoretinopathy (PVR) epiretinal membranes, but they also exhibited a dense macrophagic infiltration. In addition, three of the membranes contained multinucleated cells. Macrophages represented up to 30% of the cells present and appeared to contain large intracytoplasmic vacuoles. Similar cells were seen on the back of the posterior lens capsule in one specimen and all three capsules had posterior migration of lens epithelium. CONCLUSION The pathological findings are not simply those of PVR. The macrophage infiltration suggests that there may be a biological reaction to F6H8 which could reflect its surmised propensity to emulsify. Further investigations concerning the cellular response to this promising tamponade agent are warranted.

Expression of hypoxia-inducible factor−1α and −2α in human choroidal neovascular membranes

PurposeUp-regulation of pro-angiogenic cytokine expression occurring secondary to hypoxia in physiologic and pathophysiologic conditions is mediated by the family of transcription regulators know as hypoxia inducible factors (HIF). The present study was undertaken to investigate the expression of HIF occurring in human choroidal neovascularization (CNV) and the posterior segment of young and old eyes.MethodsSurgically excised CNV from patients with either age-related macular degeneration (AMD; nu2009=u20099), punctuate inner choroidopathy (PIC; nu2009=u20093) and young normal eyes were immunohistochemically probed with monoclonal antibodies against HIF−1α and −2α and compared to that for cell markers specific for vascular endothelial cells (CD34), macrophages (CD68), retinal pigment epithelial cells (RPE; panel cytokeratins/CK18) and VEGF. Following secondary antibody amplification, reactions were visualized with fast red chromogen.ResultsCellular immunoreactivity of membranes for HIF−2α was strong in eight out of nine AMD specimens but it was only weakly positive for HIF−1α in five specimens. In contrast, two out of three PIC specimens were weakly positive for HIF−1α but demonstrated no staining for HIF−2α. Immunohistochemical analysis revealed areas within the CNV membranes that were predominantly immunopositive for CD68 and cytokeratin indicating the presence of RPE and/or macrophages and that these cells strongly co-localized with the presence of HIF and VEGF. No immunochemical co-localization was observed with HIF and the endothelial cell marker CD34 in any membranes studied. Normal globes also demonstrated HIF−2 positivity to be predominantly localized to the central RPE rather than peripheral RPE irrespective of age of donor.ConclusionsThe localization of HIF expression supports the concept that hypoxia is a major stimulus for the development of submacular wound healing and within this context CNV is but one component of this process.

Case selection in macular relocation surgery for age related macular degeneration

Background: To date there has been no randomised controlled trial demonstrating the safety and efficacy of macular relocation surgery (MRS) for age related macular degeneration (AMD). Vision can be improved in some patients and made worse in others despite successful surgery or because of complications. Purpose: To determine which patients would benefit from MRS. Methods: Twenty nine patients with exudative AMD took part in a prospective, non-comparative, interventional study. Macular relocation surgery involved phacoemulsification, vitrectomy, 360° retinotomy, excision of choroidal neovascular membrane, and macular relocation using an infusion of 5-fluorouracil and low molecular weight heparin as adjuvant to prevent proliferative vitreoretinopathy. Patients underwent protocol refraction preoperatively and six-monthly postoperatively by designated optometrists. Preoperative fundus fluorescein angiograms were read by masked observers and the lesions were classified according to a set protocol. The main outcome measures were visual improvement, final vision of better than 20/400, reading speed, critical print size. Logistic and multiple stepwise linear regressions were used to identify independent factors which predicted the main outcomes. Results: Preoperative visual acuity (20/120 or worse) and lesion type (predominantly classic or submacular haemorrhage) were significantly associated with visual improvement (coefficient of regression Bu200a=u200a26.8, p<0.001 and Bu200a=u200a14.9 with pu200a=u200a0.045 respectively). There were no significant independent factors which predicted a final distance logMAR visual acuity of 1.3 (20/400) or any arbitrary definition of blindness. Conclusions: The study showed that it was possible to select cases that were more likely to experience an improvement in vision following MRS.

Can a preoperative bevacizumab injection prevent recurrent postvitrectomy diabetic vitreous haemorrhage

AimsTo evaluate the recurrence rate of vitreous haemorrhage (VH) in patients treated with one intravitreal bevacizumab (IVB) injection (2.5u2009mg/0.1u2009ml) before planned pars plana vitrectomy for treatment of diabetic non-clearing VH.MethodsProspective pilot study of 32 eyes of 31 consecutive diabetic patients who underwent IVB injection within 1 week before surgery for persistent VH in the presence of active proliferative diabetic retinopathy. Three masked retinal specialists graded the amount of VH from grade 0 to grade 3 with slit-lamp biomicroscopy. Main outcome measures were the rate of recurrence of the VH, improvement in visual acuity, incidence of cataract formation, and postoperative complications through a follow-up of 6 months.ResultsThe percentage of severe recurrent VH with no fundus details (grade 3) was 3% at 1 week follow-up and 3, 6, and 6% respectively at 1-, 3-, and 6-month follow-up. The mean best-corrected visual acuity (BCVA) improved from 1.6 (1/60) to 0.40 (6/15) logMAR (P=0.02) in 29 out of 32 eyes (91%). In all, 12 out of 22 (54%) phakic eyes developed cataract during the follow-up period, and 10 (31%) of them underwent cataract surgery.ConclusionsOur study suggests that IVB injection few days before planned surgery seems to be efficacious and safe as an adjuvant treatment to prevent rebleeding in eyes undergoing pars plana vitrectomy for treatment of diabetic vitreous haemorrhage. IVB facilitates the surgery and reduces the need for extensive delamination and segmentation, decreasing the possibility of significant early active postoperative VH.

Does the Presence of an Epiretinal Membrane Alter the Cleavage Plane during Internal Limiting Membrane Peeling

PURPOSEnTo determine whether the presence of a clinically and/or microscopically detectable epiretinal membrane (ERM) alters the cleavage plane during internal limiting membrane (ILM) peeling.nnnDESIGNnRetrospective, observational, immunohistochemical study of ILM specimens using archival formalin-fixed, paraffin-embedded tissue.nnnPARTICIPANTSnFifty-one patients who had had ILM excision.nnnMETHODSnFifty-one ILM specimens peeled during vitrectomy for various etiologies were examined by light microscopy. The removal of ILM was assisted using Trypan blue (n = 30), indocyanine green (n = 7), or brilliant blue G (n = 14). Monoclonal antibodies to glial fibrillary acidic protein and to neurofilament protein were used to detect glial or neuronal cells respectively on the vitreous or retinal surfaces of the ILM. Specimens were divided into 2 groups: ILM peeled for full-thickness macular hole (MH; n = 31) and ILM peeled after removal of clinically detectable ERM (n = 20).nnnMAIN OUTCOME MEASURESnPrimary outcome measure was the localization of immunohistochemical markers to neuronal or glial cells on the vitreous or retinal surfaces of ILM. The secondary outcome measure was the correlation of the results of the primary measure with the dyes used to facilitate ILM peeling.nnnRESULTSnGlial and/or neuronal cells were detected on the retinal surface of the ILM in 10 of 31 (32%) of the MH ILM specimens and in 13 of 20 (65%) of the ILM peeled after ERM excision; the difference was significant (P = 0.02). There was no association between the presence of neuronal and glial cells with the type of dye used (P = 0.2). Of the 23 ILM specimens with cells attached to the retinal surface, 21 (91%) were associated with clinical and/or histologic evidence of ERM and 2 (9%) were not. The correlation between the presence of cells on the vitreous and the retinal surfaces of ILM was high (P<0.0001).nnnCONCLUSIONSnThe findings suggest that ERM may be associated with sub-ILM changes that alter the plane of separation during ILM peeling. This study does not confirm any influence of dyes on the cleavage plane during surgery.