Louisa Wickham

Predictive clinical features and outcomes of vitrectomy for proliferative diabetic retinopathy

Objective: To study the preoperative characteristics, complications and outcomes of vitrectomy for proliferative diabetic retinopathy and to identify any factors that may predict visual outcome. Methods: Prospective study of 174 consecutive vitrectomies in 148 patients, with a minimum follow-up of 4 months. Results: 41 (27.7%) patients had a vision of <6/60 in their better eye at presentation. Posterior retinal breaks occurred in 47 (27.0%) eyes. Postoperative complications included vitreous cavity haemorrhage in 37 (22.0%) eyes, retinal detachment in five eyes (3.0%), and rubeotic glaucoma in five eyes (3.0%). 124 (74.7%) eyes improved by at least 0.3 LogMAR units, and 15 (9.0%) worsened by at least 0.3 LogMAR units. 119 (71.7%) eyes had a visual acuity of 6/60 or better, and 27 (16.3%) were counting fingers or worse. Only 16 (11.1%) patients had a vision of <6/60 in both eyes at latest follow-up. Preoperative vision in both the operated eye and the contralateral eye, macular detachment, and long-acting intraocular tamponade were independent predictors of poor postoperative vision, but this model accounted for only a small proportion of the observed variation in outcomes. Conclusions: Major complications are rare after vitrectomy for proliferative diabetic retinopathy, and >70% of eyes will regain vision of 6/60 or better. Visual outcomes remain unpredictable.

Immunopathology of intraocular silicone oil: enucleated eyes

Aims: To characterise the distribution of silicone oil in ocular tissues in globes enucleated after complicated retinal detachment, and to document the distribution and nature of any associated inflammatory response. Method: 9 enucleated globes that had previously undergone retinal detachment surgery with silicone oil and 7 control globes that had undergone enucleation after retinal detachment surgery (n = 2) or ocular trauma (n = 5) were studied. Sections were histologically examined using light microscopy to document the distribution of silicone oil in ocular tissues. Immunohistochemical analysis was carried out using the ABC technique and a panel of monoclonal and polyclonal antibodies. Electron microscopy was undertaken to observe the penetration of silicone oil in the trabecular meshwork of the anterior chamber drainage angle. Results: Silicone oil was distributed throughout the globes—notably in the iris, ciliary body, retina, trabecular meshwork and epiretinal membranes. Focal areas of intraretinal silicone were associated with disorganised retinal architecture, retinectomy sites or subretinal oil. The distribution of macrophages was closely related to the distribution of silicone oil. T and B lymphocytes were not associated with silicone oil unless additional pathology was also present—for example, cyclitic membrane or uveitis. One of the nine eyes had silicone oil present in the optic nerve. In the control globes, the inflammatory response was mediated primarily by macrophages and T lymphocytes, and was less marked than that observed in the silicone oil globes. Conclusion: This study shows that silicone oil may be sequestered in varied ocular tissues and is associated with localised inflammation mediated by macrophages.

Pilot randomised controlled trial of face-down positioning following macular hole surgery

ObjectiveThis was a pilot randomised controlled trial (RCT) to investigate the effect of post-operative face-down positioning on the outcome of macular hole surgery and to inform the design of a larger definitive study.MethodsIn all, 30 phakic eyes of 30 subjects with idiopathic full-thickness macular holes underwent vitrectomy with dye-assisted peeling of the ILM and 14% perfluoropropane gas. Subjects were randomly allocated to posture face down for 10 days (posturing group) or to avoid a face-up position only (non-posturing group). The primary outcome was anatomical hole closure.ResultsMacular holes closed in 14 of 15 eyes (93.3%; 95% confidence interval (CI) 68–100%) in the posturing group and in 9 of 15 (60%; 95% CI 32–84%) in the non-posturing group. In a subgroup analysis of outcome according to macular hole size, all holes smaller than 400 μm closed regardless of posturing (100%). In contrast, holes larger than 400 μm closed in 10 of 11 eyes (91%; 95% CI 58–99%) in the posturing group and in only 4 of 10 eyes (40%; 95% CI 12–74%) in the non-posturing group (Fishers exact test P=0.02).ConclusionPost-operative face-down positioning may improve the likelihood of macular hole closure, particularly for holes larger than 400 μm. These results support the case for a RCT.

Surgical failure following primary retinal detachment surgery by vitrectomy: risk factors and functional outcomes

Aim To identify preoperative features associated with surgical failure following vitrectomy using data collected in a large, prospective randomised controlled trial. Outcomes of patients who redetached were then examined in more detail. Methods 615 patients were analysed as part of an randomised controlled trial investigating the use of 5-fluorouracil and low-molecular-weight heparin. Treatment status had no effect on success rates and did not therefore form part of the analyses. Failure was defined as retinal redetachment within 6 months of primary vitrectomy. Univariate logistic regression analysis was used to assess association between failure and putative risk factors (age, pathological myopia, intraocular pressure, vitreous haemorrhage, previous lens extraction, uveitis, number of retinal quadrants detached, number and distribution of retinal breaks, and grade C proliferative vitreoretinopathy (PVR)). Additional characteristics of patients were then elucidated including number of operations required to achieve retinal reattachment, surgical techniques used and final logMAR visual acuity. Results 96 patients (15.6%) redetached following surgery, and 37 failed due to PVR. Surgical failure was associated with number of retinal quadrants detached (OR per increase, 1.69 (1.33 to 2.15) p<0.001) and grade C PVR (OR 3.98 (1.47 to 10.73) p=0.006). Inferior breaks were not identified as a risk factor (p=0.602). Repeat retinal detachment surgery showed a trend towards reduced visual acuity at 6 months providing PVR did not develop. PVR resulted in a significant deterioration in visual acuity. Conclusions The extent of retinal detachment and preoperative PVR are risk factors for surgical failure following vitrectomy for primary retinal detachment. PVR was again confirmed as the major factor influencing visual outcomes.

Using spectral-domain optical coherence tomography imaging to identify the presence of retinal silicone oil emulsification after silicone oil tamponade.

Purpose: To describe small hyperreflective areas using spectral-domain optical coherence tomography (SD-OCT) imaging in eyes that have had silicone oil tamponade. Methods: Retrospective case series of 11 eyes of 11 patients. The authors retrospectively identified patients who underwent vitrectomy and silicone oil tamponade secondary to a rhegmatogenous retinal detachment (nine patients), panuveitis with retinal necrosis (one patient), or recurrent full-thickness macular hole surgery (one patient) who had manifestations of silicone oil emulsion on SD-OCT imaging. Patients were monitored during the postoperative period by clinical examination and using SD-OCT. A model eye in which emulsified silicone oil had been injected in the anterior chamber was used to obtain anterior segment SD-OCT images for comparison. Results: The mean age of our patients was 50 years (range, 39–76 years). In eight eyes, the SD-OCT examination was carried out after silicone oil removal, and in three eyes, the SD-OCT examination was carried out with the oil in situ. Of the nine eyes treated for rhegmatogenous retinal detachment, five had a relieving retinectomy for advanced anterior proliferative vitreoretinopathy or for traumatic retinal incarceration (one eye). The eye treated for full-thickness macular hole had a vitrectomy, internal limiting membrane peel, and silicone oil injection for recurrent macular hole. Ten eyes showed hyperreflective, spherical, tiny droplets using SD-OCT imaging. These were thought to represent silicone oil droplets intraretinally or underneath epiretinal membranes, and one eye showed hyperreflective areas subretinally (retina detached). One additional patient was found to have tiny intravitreal silicone oil droplets after silicone oil removal. Similarly, the silicone oil appeared as multiple hyperreflective spherical droplets as detected by SD-OCT. Anterior segment studies of silicone oil emulsification in the experimental model revealed a similar appearance to that seen with in vivo SD-OCT imaging. Conclusion: The authors have found small hyperreflective areas intraretinally, subretinally, and underneath epiretinal membranes on SD-OCT in eyes that have had silicone oil tamponade for a variety of indications. The authors have seen a similar appearance when silicone oil emulsification is examined in vivo. The authors conclude that the hyperreflective areas are likely (but not certain) to be very small bubbles of emulsified silicone. Further studies are required to determine the incidence, clinicopathologic, and functional significance of probable silicone oil emulsification and deposition within the retinal layers.

A pilot randomised controlled trial comparing the post-operative pain experience following vitrectomy with a 20-gauge system and the 25-gauge transconjunctival system.

Aims: To compare post-operative pain following 25-gauge (25G) and 20-gauge (20G) vitrectomy in the first week following surgery. Methods: The study was a pilot randomised controlled trial with patients masked to the treatment allocation. Post-operative pain was assessed using both a visual scale and verbal pain scores for 1 week following surgery. Additional data collected included intraocular pressure (IOP), time taken to perform the surgical procedure, per-operative and post-operative complications, and dropout rates. Results: Forty patients were recruited for the study: 21 randomised to 20G vitrectomy and 19 to 25G. In the first 12 h following surgery, presence of significant post-operative pain (defined as >1 cm on a visual analogue scale) was similar in both 20G (50%) and 25G (53%) patients. In the first week following surgery, 38 of the 527 scores (7.2%) were >1 (median 2.1, IQR 1.3–3) cm; however, there was evidence that “significant pain” was experienced more commonly in the 20G group. There was no statistical difference in the time taken to complete the surgical procedure, although in the 25G group the time from first incision to the start of vitrectomy was significantly shorter (p = 0.043) and in the 20G group the time taken to complete the vitrectomy was less (p = 0.047). Post-operative hypotony (IOP <6 mmHg) was observed in 25% of patients in the 25G group. No patients required additional surgery for hypotony. Conclusion: There was evidence that 25G resulted in less patient discomfort. However, pain was not a prominent feature in either group. We failed to find a significant advantage in 25G for patients or surgeons.

Retinal detachment repair by vitrectomy: simplified formulae to estimate the risk of failure

Aim Devise simplified formulae, using preoperative clinical data, to give risk estimates of (1) failure and (2) proliferative vitreoretinpathy (PVR) following primary retinal detachment repair by vitrectomy. Methods 641 patients were analysed as part of an RCT investigating use of 5-fluorouracil and low-molecular-weight heparin. Treatment status had no effect on success rates and did not therefore form part of the analyses. Preoperative risk factors for surgical failure and for PVR within 6 months of retinal detachment surgery were identified, and a multiple variable logistic regression model developed. Further analyses were performed to devise a simple points system to produce risk estimates of failure. Results Three risk factors were related to failure—previous lens extraction (p=0.046), grade C PVR (p=0.039) and extent of detachment (p<0.001). Three risk factors were also related to failure due to PVR—vitreous haemorrhage (p=0.088), grade C PVR (p=0.044) and extent of detachment (p<0.001). There was good agreement between risk estimates produced by the points system and those calculated directly using a multivariate regression model. The points-system model gave an area under the receiver operating characteristic curve of 0.658. The receiver operating characteristic curve for the PVR model gave an area under the curve of 0.8399 suggesting greater diagnostic value. Conclusions A simple points system may be used as a clinical guide to identify patients at higher risk of failure following retinal detachment repair by vitrectomy. This may help clinicians select appropriate surgical approaches and stratify cases in research and surgical training.

Glial Cell Changes of the Human Retina in Proliferative Vitreoretinopathy

Retinal detachment initiates a complex series of cellular and molecular changes. Because of the difficulty in obtaining retinal tissue from patients with retinal detachments, most investigations of the cellular changes following retinal detachment have been carried out on animal models. Animal experiments suggest that the cellular response to retinal detachment may be broadly described as; partial dedifferentiation of retinal pigment epithelium cells, proliferation and migration of retinal pigment epithelium cells into the subretinal space, degeneration of the photoreceptor outer segments and synaptic terminals, photoreceptor cell death, structural remodelling of second-order and third-order retinal neurons, proliferation of all non-neuronal cell types within the retina and Muller cell hypertrophy leading to glial scar formation. Each of these stages are considered in turn and related to findings in human proliferative vitreoretinopathy.

Clinicopathological case series of four patients with inherited macular disease

PURPOSE To correlate the phenotype of four patients with inherited macular disease with the immunohistopathology of retinal tissue collected at the time of retinal pigment epithelium (RPE)-choroidal transplantation. METHODS A clinicopathologic case series describing the phenotype of four patients, including confocal immunohistochemistry and electron microscopy (EM), and the results of genetic testing. RESULTS In Case 1, electrophysiology showed only macular dysfunction. Confocal microscopy revealed minor abnormalities. EM showed abnormal cone inner segments with swollen mitochondria. In case 2 (R172W mutation in RDS), electrophysiology demonstrated generalized cone system dysfunction with severe macular involvement. Peripherin labeling of outer segments was nonuniform, and EM showed discs arranged in whorllike structures. Case 3 showed severe central macular dysfunction on multifocal electroretinogram (ERG). Peripherin staining was irregular and disorganized. EM revealed abnormal inner segment morphology, particularly in rods, and disorganized irregular outer segments. Case 4 had localized central macular dysfunction on multifocal ERG. Confocal microscopy was grossly normal, with evidence of early redistribution of cone opsin to the inner segment. EM showed variable rod morphology and normal cones. CONCLUSIONS RPE transplantation provides a unique opportunity to gain insight into retinal disorders by enabling phenotypic correlation with the immunohistopathology of retinal tissue collected during surgery.

Ranibizumab pretreatment in diabetic vitrectomy a pilot randomised controlled trial (the RaDiVit study)

PurposeOur aim was to evaluate the impact of intravitreal ranibizumab pretreatment on the outcome of vitrectomy surgery for advanced proliferative diabetic retinopathy. The objective was to determine the feasibility of a subsequent definitive trial and estimate the effect size and variability of the outcome measure.Patients and methodsWe performed a pilot randomised double-masked single-centre clinical trial in 30 participants with tractional retinal detachment associated with proliferative diabetic retinopathy. Seven days prior to vitrectomy surgery, participants were randomly allocated to receive either intravitreal ranibizumab (Lucentis, Novartis Pharmaceuticals UK Ltd, Frimley, UK) or subconjunctival saline (control). The primary outcome was best-corrected visual acuity 12 weeks following surgery.ResultsAt 12 weeks, the mean (SD) visual acuity was 46.7 (25) ETDRS letters in the control group and 52.6 (21) letters in the ranibizumab group. Mean visual acuity improved by 14 (31) letters in the control group and by 24 (27) letters in the ranibizumab group. We found no difference in the progression of tractional retinal detachment prior to surgery, the duration of surgery, or its technical difficulty. Vitreous cavity haemorrhage persisted at 12 weeks in two of the control group but none of the ranibizumab group.ConclusionRanibizumab pretreatment may improve the outcome of vitrectomy surgery for advanced proliferative diabetic retinopathy by reducing the extent of post-operative vitreous cavity haemorrhage. However, the effect size appears to be modest; we calculate that a definitive study to establish a minimally important difference of 5.9 letters at a significance level of P<0.05 would require 348 subjects in each arm.