David G. Charteris

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.

The epidemiology of rhegmatogenous retinal detachment: geographical variation and clinical associations.

Aims/Background Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition. Obtaining an accurate estimate of RRD incidence in the population is essential in understanding the healthcare burden related to this disorder. Methods A systematic review of all population-based epidemiology studies of RRD published between January 1970 and January 2009 from Medline database searches was performed. Results RRD incidence demonstrates significant geographical variation and its incidence has been reported to be between 6.3 and 17.9 per 100 000 population. For studies with a sample size >300 the median annual incidence per 100 000 population was 10.5 (IQR 8.1–13.2) and the mean proportion of bilateral RRD was 7.26%. Overall, the mean prevalence of lattice degeneration was 45.7±20.3% and myopia was 47.28±12.59%. Conclusions Estimates of RRD incidence have varied threefold, but inclusion criteria and other design features have differed across studies making direct comparisons difficult. The overall incidence of RRD is not yet well established: more incidence studies of adequate methodology are needed to explore temporal changes in incidence. RRD incidence varies with ethnicity and is strongly associated with increasing age, myopia and certain vitreo-retinal degenerations. Due to changes in cataract surgery trends, the proportion of pseudophakic RRD presenting to specialised centres appears to be increasing.

Proliferative vitreoretinopathy—developments in adjunctive treatment and retinal pathology

Proliferative vitreoretinopathy (PVR) remains a difficult management problem despite advances in vitreoretinal surgery. There is still a significant incidence of PVR in rhegmatogenous retinal detachment and other forms of retinal disease. Surgery for PVR now has a high anatomical success rate although visual results are often disappointing. The use of adjunctive treatments to prevent cellular proliferation holds promise for the prevention of PVR or recurrences after surgery. Control of proliferation and strategies aimed at improving visual outcome are important areas of future research in PVR and other forms of retinal disease. Studies of the intraretinal and peri-retinal pathology of PVR have demonstrated characteristic changes which may have a significant influence on visual outcome and surgical management.

Animal models of retinal detachment and reattachment: identifying cellular events that may affect visual recovery

Retinal detachment continues to be a significant cause of visual impairment, either through the direct effects of macular detachment or through secondary complications such as subretinal fibrosis or proliferative vitreoretinopathy. Animal models can provide us with an understanding of the cellular mechanisms at work that account for the retinopathy induced by detachment and for the generation of secondary effects. As we understand the mechanisms involved, animal models can also provide us with opportunities to test therapeutic agents that may reduce the damaging effects of detachment or improve the outcome of reattachment surgery. They may also reveal information of use to understanding other causes of blindness rooted in retinal defects or injuries. Understanding the effects of detachment (and reattachment) are likely to become even more important as surgeons gain skills in subretinal surgical techniques and macular translocation, both of which will generate short-lived detachments. Here we discuss the fundamental events that occur after detachment, present changes associated with reattachment, and discuss retinal changes that may affect the return of vision.

Matrix metalloproteinases and their natural inhibitors in fibrovascular membranes of proliferative diabetic retinopathy

AIM To examine epiretinal membranes of proliferative diabetic retinopathy (PDR) for the presence of selective matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs), in order to determine whether neovascularisation and fibrosis, characteristic of this complication of diabetes mellitus, are associated with specific anomalies of MMP or TIMP expression. METHODS The presence of selected MMPs and TIMPs was investigated in 24 fibrovascular epiretinal membranes of PDR, and the findings compared with that observed in 21 avascular epiretinal membranes of proliferative vitreoretinopathy (PVR) and five normal retinas. Specimens were examined for deposition of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase A (MMP-2), gelatinase B (MMP-9), and three tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, and TIMP-3). RESULTS The results showed that unlike normal retina, which constitutively expresses MMP-1 and TIMP-2, a large proportion of PDR membranes (> 62%) stained for MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, and TIMP-3. There were no differences in the expression of these molecules when compared with PVR membranes. A characteristic staining for MMP-9 was observed within the perivascular matrix of PDR membranes, and there was a significant increase in TIMP-2 expression by PDR membranes (p= 0.036) when compared with PVR membranes. CONCLUSIONS The findings that MMPs involved in degradation of fibrovascular tissue matrix, as well as TIMP-1 and TIMP-2, are found in a large proportion of PDR membranes, and that their expression does not differ from that of PVR membranes, suggest the existence of common pathways of extracellular matrix degradation in pathological processes leading to retinal neovascularisation and fibrosis.

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.

Proliferative Vitreoretinopathy Lymphocytes in Epiretinal Membranes

BACKGROUND To investigate the potential contribution of inflammatory and immune-mediated processes contributing to the pathogenesis of proliferative vitreoretinopathy (PVR), an immunohistochemical study was undertaken to characterize the infiltrating inflammatory cells in epiretinal membranes surgically removed from the eyes of patients with PVR. METHODS Twenty-one epiretinal membranes obtained surgically from eyes with PVR complicating rhegmatogenous retinal detachment were studied immunohistochemically using the ABC technique and a panel of monoclonal and polyclonal antibodies. RESULTS T lymphocytes were found in 18 of the 21 specimens and generally constituted a small percentage of the total cell number. CD4+ T cells were found in 14 of the 18 membranes containing T cells. Three of six frozen membranes contained T cells that were positive for the interleukin-2 receptor. In 5 of 16 membranes studied, cells positive for the macrophage/monocyte marker were found. No B lymphocytes or neutrophils were identified, and there were no deposits of complement or immunoglobulins. Positive staining for the class II MHC antigen HLA-DR was found in 7 of the 21 membranes, a result that was more consistent in frozen than in fixed tissues. CONCLUSION The study suggests that T lymphocytes are present in PVR epiretinal membranes and may be activated. These cells have the potential to play a role in the pathobiology of PVR.

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.

Macular hole surgery without prone positioning

PurposeTo investigate the role of vitrectomy without prone posturing in the anatomic and functional outcome of macular hole surgery (MHS).MethodsForty-one consecutive eyes of 41 patients with stage II–IV full-thickness macular holes underwent pars plana vitrectomy and 16% C3F8 tamponade. In 25 cases posturing group (P), subjects were instructed to assume prone positioning for 10 days postoperatively, whereas in 16 cases non-posturing group (NP) patients were advised to avoid lying supine but no other posturing instructions were given. Preoperative, intraoperative and postoperative clinical data were collected, with macular hole closure rate and change in LogMAR visual acuity, contrast sensitivity, metamorphopsia, and 25-Visual Function Questionnaire (VFQ-25) being the primary outcome measures.ResultsOver a mean follow-up of 4.2±1.2 months, anatomical hole closure was noted in 22/25 (88%) and 14/16 (87.5%) in groups P and NP respectively. Visual acuity improved by a mean of eight letters and there was no significant difference in the two groups (P=0.724). Similarly, postoperative prone posturing did not have an effect on the final contrast sensitivity, metamorphopsia, and VFQ-25 composite scores (P=0.238, P=0.472, and P=0.87, respectively). However, eyes in group NP developed significantly more severe cataract in the early postoperative period (P=0.02).ConclusionsProne posturing following MHS provides no functional or anatomic benefit but it is associated with slower progression of cataract. Combined phacovitrectomy without face down positioning may be considered for all phakic patients undergoing MHS.

Visual function and quality of life following vitrectomy and epiretinal membrane peel surgery

Aim: To investigate the effect of epiretinal membrane (ERM) peel on patients’ health related quality of life (HR-QOL) and to explore the association between self reported HR-QOL and conventional measures of visual function. Methods: The National Eye Institute 25 Item Visual Function Questionnaire (VFQ-25) and the 36 Item Short-Form Health Survey (SF-36) were self administered by 20 patients before and 4 months following surgery. Preoperative and postoperative data collected included logMAR near and distant visual acuity (VA), contrast sensitivity, and metamorphopsia. Questionnaire scores were compared preoperatively and postoperatively and their correlation with traditional methods of visual function evaluation analysed. Results: Postoperatively there was no significant improvement in mean logMAR VA. However, eight (40%) subjects improved by two or more ETDRS lines and nine eyes (45%) reached a final VA of 6/18 or better. Metamorphopsia decreased significantly (p = 0.019) and there was significant improvement in VFQ-25 mean scores for the general vision (p = 0.03), distance activities (p = 0.05), and composite score (p = 0.03). Baseline binocular VA was significantly correlated with baseline VFQ-25 composite score (r = 0.631, p = 0.004). Conclusions: ERM surgery appears to improve patients’ subjective perception of visual function as indicated by higher composite scores in VFQ-25 and improved metamorphopsia in the absence of significant improvement in mean logMAR VA.