G. W. Aylward

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

PURPOSE To 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. DESIGN Prospective randomized, double-masked, placebo controlled trial. PARTICIPANTS One 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. METHOD Results of standard surgery with 5-FU and LMWH therapy or placebo were compared at the 6-month follow-up. MAIN OUTCOME MEASURES Development of postoperative PVR, retinal reattachment at 6 months after surgery, single operation reattachment rate, number of reoperations, and best-corrected visual acuity. RESULTS There 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. CONCLUSIONS There 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.

Retinal pigment epithelium translocation after choroidal neovascular membrane removal in age-related macular degeneration

PURPOSE To test the feasibility of a new surgical technique and to assess visual function over the translocated retinal pigment epithelium (RPE) cells in patients operated on for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). DESIGN Retrospective, noncomparative, interventional case series. PARTICIPANTS Nine patients with previously untreated exudative ARMD underwent surgical excision of the subfoveal CNV with RPE translocation and were observed for 12 to 32 months. METHODS The surgery consisted of a standard three-port pars plana vitrectomy, excision of the CNV, and RPE translocation. Pre- and postoperative ocular examination included best-corrected visual acuity measurement, fundus color stereo photography, and fundus fluorescein angiography. Optical coherence tomography and confocal laser scanning ophthalmoscopy (cLSO) were performed after surgery. A crossfixation target and a single-point flashing light were projected on different areas of the posterior pole using a cLSO. Photopic 10 to 2 perimetry, photopic fine matrix mapping, and cLSO microperimetry were also performed after surgery in six patients. MAIN OUTCOME MEASURES Optical coherence tomography cross-sectional scans and cLSO RPE autofluorescence were recorded to detect the presence of viable translocated RPE. Visual acuity, fixation, photopic 10 to 2 perimetry, photopic fine matrix mapping, and cLSO microperimetry were used to test central visual function. RESULTS Retinal pigment epithelium was translocated successfully at the time of CNV removal from the edge of the RPE defect to a subfoveal location in seven of nine patients. One patient experienced proliferative vitreoretinopathy, but significant hemorrhage was not a feature. Optical coherence tomography showed the translocated RPE as an area of increased optical reflectivity with optical shadowing external to it. Confocal laser scanning ophthalmoscopy showed autofluorescence of the translocated RPE. The crossfixation target was seen when projected on the translocated RPE. During eccentric fixation, the patients could see a flashing point-target projected on the translocated RPE. Photopic 10 to 2 perimetry, photopic fine-matrix mapping, and cLSO microperimetry showed the presence of central visual function. CONCLUSIONS The authors propose that translocation of RPE at the time of CNV removal, from the edge of the RPE defect to a subfoveal location, may have a role in the surgical management of ARMD.

Risk factors for proliferative vitreoretinopathy after primary vitrectomy: a prospective study

AIM To assess clinical variables and vitreous protein as risk factors for the development of postoperative proliferative vitreoretinopathy (PVR). METHODS A prospective study was conducted on 140 patients with a rhegmatogenous retinal detachment in whom a primary vitrectomy was performed. 12 clinical variables were recorded and vitreous samples obtained for measurement of protein concentration. Univariate and multivariate logistic regression analysis was used to determine the risk factors for PVR. RESULTS Complete data were available for 136 of 140 patients. 40 of the 136 patients (29.4%) developed postoperative PVR. Univariate regression revealed that significant (p<0.05) risk factors included aphakia, presence of preoperative PVR, size of detachment, the use of silicone oil, and high vitreous protein level. Multivariate regression analysis revealed only aphakia (odds ratio 2.72), the presence of preoperative PVR (odds ratio 3.01), and high vitreous protein concentration (odds ratio 1.11) to be significant (p<0.05) independent, predictive risk factors for the development of PVR. CONCLUSIONS This study has shown that the significant risk factors for PVR are preoperative PVR, aphakia, and high vitreous protein levels. Two models (clinical factors only and clinical factors and vitreous protein) were constructed to predict the probability of developing postoperative PVR and may be used to identify those at risk for possible intravitreal pharmacological treatment.

Results of primary retinal reattachment surgery : A prospective audit

Purpose: To define the current success rate of primary retinal detachment repair at one centre.Methods: One hundred and fifty-three consecutive patients undergoing surgery for primary retinal detachments over a 6 month period were studied prospectively. Data sheets were completed immediately after surgery and at final follow-up. One hundred and twenty-seven patients completed 6 months of follow-up. Follow-up data on the remainder were obtained from the referring unit or directly from the patients by telephone. The term primary success was used to describe persisting retinal reattachment after a single operation. Multiple logistic regression was carried out to establish factors associated with failure.Results: One hundred and twenty-three patients (80%) had persisting retinal reattachment after a single procedure. Of the 30 patients who required further surgery, in 5 the retina remained detached at final follow-up. The final anatomical success rate was 97%. New or missed breaks were the major causes of failure of primary surgery. Failure of primary surgery was associated with the presence of highly elevated breaks (β = 0.11, p = 0.03). No other pre-operative factors appeared to predict failure to reattach the retina.Conclusions: Comparison of these results with those of a previous audit carried out at this hospital 23 years ago suggests little improvement in the success rate of primary surgery (75% vs 80%). The improvement in final retinal reattachment has been rather greater (from 88% to 97%). The major impact of recent technical advances in retinal reattachment surgery has been on the success rate of reoperations after failed primary surgery.

How to predict proliferative vitreoretinopathy: a prospective study.

PURPOSE To determine prospectively the accuracy of a predictive risk formula for the development of postoperative proliferative vitreoretinopathy (PVR) when applied in a clinical setting. DESIGN Prospective noncomparative interventional case series. PARTICIPANTS Two hundred nineteen subjects undergoing primary vitrectomy for rhegmatogenous retinal detachment were studied. METHOD By 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. OUTCOME MEASURES Development of postoperative PVR as defined by the updated the Retina Society Classification. RESULTS Complete 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). CONCLUSIONS Our study has shown that using a clinical model it is possible to identify subjects at greater risk of PVR developing after primary vitrectomy.

Visual field loss following vitrectomy for stage 2 and 3 macular holes.

AIM--To describe the phenomenon of peripheral field loss following routine pars plana vitrectomy for stage 2 and 3 full thickness macular hole and to investigate the underlying mechanism. METHODS--Five patients, who reported peripheral field defects after apparently uncomplicated vitrectomy, posterior cortical vitreous peeling, and perfluoropropane (C3F8) gas tamponade, were studied retrospectively with slit-lamp biomicroscopy, automated and kinetic perimetry, fundal fluorescein angiography, focal electroretinography (ERG), and colour contrast sensitivity (CCS) testing. RESULTS--All five patients, who were between 50 and 73 years of age, reported an inferotemporal field defect following resolution of the intraocular gas bubble. In all eyes, the scotomata encroached to within 20 degrees to 30 degrees of fixation and to within 5 degrees to 15 degrees of the blind spot. In one eye, a partial altitudinal component was evident. All scotomata subsequently remained stable and three eyes developed subtle segmental nasal disc pallor and nerve fibre loss corresponding to the field defect. CCS testing revealed absent colour contrast in the scotomatous area, in the presence of a preserved focal quadrantic flash ERG, compared with normal CCS protan thresholds and focal ERGs in unaffected quadrants, indicating preserved outer retinal function in the area of the scotoma. CONCLUSIONS--These observations support the hypothesis that field defects occur as a result of retinal nerve fibre layer damage. It is proposed, on the basis of intraoperative observations and other evidence, that the most likely site of nerve fibre damage is at the nasal portion of the optic nerve rim or peripapillary retina, probably due to traction during cortical vitreous peeling.

Silicone oil concentrates fibrogenic growth factors in the retro-oil fluid

Aim: To determine whether silicone oil concentrates protein and growth factors in the retro-oil fluid. Methods: A laboratory analysis of intraocular fluid and vitreous specimens obtained from patients undergoing removal of silicone oil, revision vitrectomy, or primary vitrectomy for macular hole, proliferative vitreoretinopathy (PVR), or retinal detachment. Patients were prospectively recruited from routine vitreoretinal operating lists. Vitreous cavity fluid and vitreous samples were analysed for the presence of transforming growth factor beta (TGF-β2), basic fibroblast growth factor (bFGF), interleukin 6 (IL-6), and total protein using either commercially available enzyme linked immunosorbent assays (ELISA) or protein assay kits. Results: The median levels of bFGF, IL-6, and protein in the retro-oil fluid were raised (p<0.05) compared to all the other vitreous and vitreous cavity fluid samples. bFGF, IL-6, and protein levels were raised in PVR vitreous compared to non-PVR vitreous. TGF-β2 levels were not significantly raised in retro-oil fluid or in PVR vitreous. Conclusions: The concentration of fibrogenic (bFGF) and inflammatory (IL-6) growth factors and protein is raised in retro-silicone oil fluid. This may contribute to the process of retro-oil perisilicone proliferation and subsequent fibrocellular membrane formation.

Bilateral acute retinal necrosis and herpes simplex type 2 encephalitis in a neonate

Editor,—Acute retinal necrosis (ARN) is a rapidly progressing, sometimes devastating, retinitis associated with the herpes virus family. First described in 1971,1 it is diagnosed by the clinical triad of progressive peripheral retinal necrosis, occlusive vasculopathy, and vitreous inflammation.2 The association of herpetic encephalitis with ARN has been described in adults.34 Herpes simplex virus type 2 (HSV-2) has also been recognised as one of the causative agents of the ARN syndrome, particularly in Japan.5 It has been suggested that ARN in patients less than 25 years of age is likely to be caused by HSV-2.6 We present a case of bilateral ARN (BARN) in a neonate with HSV-2 encephalitis. ### CASE REPORT A 25 day old infant presented with a 4 day history of lethargy, poor feeding, and coughing. …

Effects of single, short-term exposures of human retinal pigment epithelial cells to thiotepa or 5-fluorouracil: implications for the treatment of proliferative vitreoretinopathy.

AIM To investigate the effects of single, short term (5 or 30 minutes) exposures to thiotepa or 5-fluorouracil (5-FU) on collagen lattice contraction and retinal pigment epithelial (RPE) cell proliferation. METHODS For collagen contraction studies, RPE cells seeded into free floating type I collagen lattices were exposed to single 5 or 30 minute treatments with thiotepa (0.06–4 mg/ml), or 5-FU (0.25–25 mg/ml), or phosphate buffered saline alone as a control. For proliferation studies, RPE cell monolayers were similarly exposed to these agents. The degree of contraction, effects on cell number, and viability were determined up to 14 days after treatment. RESULTS Contraction of collagen lattices containing RPE cells and proliferation of RPE cells were significantly inhibited (p<0.05) by thiotepa and 5-FU at concentrations above 0.06 mg/ml and 0.25 mg/ml respectively (for both 5 and 30 minute treatments), compared with controls. Cell death did not occur except for exposure of the RPE cells in collagen lattices to the highest concentration of thiotepa (4 mg/ml). CONCLUSION It was concluded that single 5 or 30 minute exposures to thiotepa or 5-FU significantly inhibited collagen contraction and the proliferation of RPE cells. These findings suggest that short, single, non-toxic exposures to thiotepa or 5-FU which can be reproduced clinically may be useful in the modulation of proliferative vitreoretinopathy.

Retinal pigment epithelium translocation and central visual function in age related macular degeneration: preliminary results

Purpose: To test the feasibility of a new surgical technique, and to assess visual function over the translocated retinal pigment epithelium (RPE) cells in patients operated upon for subfoveal choroidal neovascularization (CNV) secondary to age-related maculardegeneration (AMD).Materials and methods: Six patients presenting previouslyuntreated exudative AMD underwent surgical excision of the subfoveal CNV with RPE translocation and were followed from 1 to 10.5 months. The surgery consisted of a standard three port pars plana vitrectomy (TPPPV), excision of the CNV and RPE translocation. Pre and post-operative ocular examination included best-corrected visual acuity measurement, fundus color stereo photography and fundus fluoresceinangiography. Optical coherence tomography (OCT) and confocal laser scanning ophthalmoscopy (cLSO) were performed post-operatively. A cross fixation target and a single-point flashing light were projected on different areas of the posterior pole using a cLSO. Photopic 10-2 perimetry, photopic fine matrix mapping, cLSO microperimetry were also performed pre and post-operatively in four patients. OCTcross-sectional scans and cLSO RPE autofluorescence were recorded to detect the presence of viable translocated RPE. Visual acuity, fixation, photopic 10-2 perimetry, photopic fine matrix mapping and cLSO microperimetry were tested for the presence of central visual function. Results: RPE could be effectively translocated at thetime of CNV removal from the edge of the RPE defect to a subfoveal location. OCT showed the translocated RPE as an area of increased optical reflectivity with optical shadowing external to it. cLSO showed autofluorescence of the translocated RPE. The cross fixation target was seen when projected on the translocated RPE. During eccentricfixation, the patients could see a flashing point-target projected on the translocated RPE. Photopic 10-2 perimetry, photopic fine matrix mapping and cLSO microperimetry showed presence of central visual function.Conclusions: The authors propose that translocationof RPE at the time of CNV removal, from the edge of the RPE defect to a subfoveal location, may have a role in the surgical management of AMD.