Ozurdex(R) (a slow-release dexamethasone implant) in proliferative vitreoretinopathy: study protocol for a randomised controlled trial

Proliferative vitreoretinopathy (PVR) is the commonest cause of late anatomical failure in rhegmatogenous retinal detachment. Visual and anatomical outcomes remain poor despite advances in vitreoretinal surgical techniques with reported primary failure rates of up to nearly 50%. Numerous adjunctive medications have been evaluated in clinical trials with no agent gaining widespread acceptance and use.This study was designed to investigate the benefits of using a slow-release dexamethasone implant delivered intra-operatively in patients undergoing vitrectomy surgery for retinal detachment with established PVR.Methods/design: For the study, 140 patients requiring vitrectomy surgery with silicone oil for retinal detachment with established PVR will be randomised to receive either standard treatment or study treatment in a 1:1 treatment allocation ratio. Both groups will receive the standard surgical treatment appropriate for their eye condition and routine peri-operative treatment and care, differing only in the addition of the supplementary adjunctive agent in the treatment group. The investigated primary outcome measure is stable retinal reattachment with removal of silicone oil without additional vitreoretinal surgical intervention at 6 months

Postretinal Detachment Retinal Displacement: How Best to Detect It?

PURPOSE: The reported incidence of postretinal detachment (RD) macular displacement varies markedly (14-72%). This may in part be due to the imaging modalities used. We compared the ability of 2 types of fundus autofluorescence (FAF) imaging modalities to detect this phenomenon. METHODS: Prospective study of 70 eyes with macula-involving RDs. 8 weeks postoperatively, patients underwent FAF imaging with 2 machines: a confocal scanning laser ophthalmoscope (cSLO) and a digital fundus camera (FC). Images were graded for the presence of hyperautofluorescent RPE (retinal pigment epithelium) ghost vessels, indicative of retinal displacement, by 2 masked, independent graders. RESULTS: In total, 87.1% of FC images were gradable versus 88.6% of cSLO images. Retinal displacement was detectable in 61.4% of FC images versus 52.8% of cSLO images. Vessel shift often appeared more autofluorescent on FC imaging, but choroidal vessels were more visible. Cohen's agreement between the imaging modalities was 0.50, rated as moderate agreement. For both imaging modalities, the inter- and intragrader agreement was substantial, representing good test-retest reliability. CONCLUSIONS: Detection of post-RD retinal displacement was similar between FC and cSLO FAF imaging, with only moderate agreement between both modalities

A pilot study of intraocular use of intensive anti-inflammatory; triamcinolone acetonide to prevent proliferative vitreoretinopathy in eyes undergoing vitreoretinal surgery for open globe trauma; the Adjuncts in Ocular Trauma (AOT) Trial: study protocol for a randomised controlled trial

Eyes sustaining open globe trauma (OGT) is a group at high risk of severe visual impairment. Proliferative vitreoretinopathy (PVR) is the commonest cause of retinal redetachment in these eyes and is reported to occur in up to 45% of cases. Intensive anti-inflammatory agents have been shown to be effective at modifying experimental PVR and to be well tolerated clinically.The Adjuncts in Ocular Trauma (AOT) Trial was designed to investigate the benefits of using intensive anti-inflammatory agents (intravitreal and sub-Tenon's triamcinolone, oral flurbiprofen and guttae prednisolone 1.0%) perioperatively in patients undergoing vitrectomy surgery following open globe trauma

Widefield Spectral-Domain Optical Coherence Tomography Imaging of Peripheral Round Retinal Holes With or Without Retinal Detachment

PURPOSE: To describe the widefield spectral-domain optical coherence tomography features of peripheral round retinal holes, with or without associated retinal detachment (RD). METHODS: Retrospective, observational study of 28 eyes with peripheral round retinal holes, with and without RD. Patients underwent imaging with a widefield 50-degree spectral-domain optical coherence tomography (Heidelberg Engineering, Germany) and Optos ultra-widefield imaging systems (Optos, United Kingdom). RESULTS: Vitreous attachment at the site of the retinal hole was detected in 27/28 (96.4%) cases. Cases were split into three groups: RHs with RD (n = 12); RHs with subretinal fluid (n = 5), and flat RHs (n = 11), with minimal or no subretinal fluid. 91.6% retinal holes associated with subretinal fluid or RD had vitreous attachment at the site of the hole. Eighty percent had vitreous attachment at both edges of the retinal hole, in a U-shape configuration, which appeared to exert traction. By contrast, flat retinal holes had visible vitreous attachment only at one edge of the retinal hole in 45.4%. CONCLUSION: Vitreous attachment was commonly seen at the site of round retinal holes. Vitreous attachment at both edges of the retinal hole in a U-shape configuration was more commonly seen at holes associated with subretinal fluid or RD

Slow-Release Dexamethasone in Proliferative Vitreoretinopathy: A Prospective, Randomized Controlled Clinical Trial

Purpose To test the hypothesis that adjunctive slow-release dexamethasone implant (Ozurdex; Allergan Inc, Irvine, CA) can improve the outcomes of vitreoretinal surgery for established proliferative vitreoretinopathy (PVR). Design A 2-year, single-center, prospective, participant- and surgeon-masked randomized controlled clinical trial (EudraCT No. 2011-004498-96). Participants A total of 140 patients requiring vitrectomy surgery with silicone oil for retinal detachment with established PVR (Grade C) were randomized to standard (control) or study treatment (adjunct) in a 1:1 allocation ratio. Methods Intraoperatively, the adjunct group received an injection of 0.7 mg of slow-release dexamethasone (Ozurdex) at the time of (1) vitrectomy surgery and (2) silicone oil removal. The control group received standard care. Main Outcome Measures Primary outcome measure was the proportion of patients with a stable retinal reattachment with removal of silicone oil without additional vitreoretinal surgical intervention at 6 months. Secondary outcomes included (1) final visual acuity (VA) (median and Early Treatment Diabetic Retinopathy Study [ETDRS] of 55 letters or better); (2) cystoid macular edema (CMO), foveal thickness, and macular volume; (3) development of overt PVR recurrence; (4) complete and posterior retinal reattachment; (5) tractional retinal detachment; (6) hypotony/increased intraocular pressure (IOP); (7) macula pucker/epiretinal membrane; (8) cataract; and (9) quality of life. Results All 140 patients were recruited within 25 months of study commencement; 138 patients had primary outcome data. Primary outcome assessment showed similar results in anatomic success between the 2 groups (49.3% vs. 46.3%, adjunct vs. control; odds ratio, 0.89; 95% confidence interval, 0.46–1.74; P = 0.733). Mean VA at 6 months was 38.3 ETDRS letters and 40.2 letters in the adjunct and control groups, respectively. Secondary anatomic outcomes (complete/posterior reattachment rates and PVR recurrence) were comparable between the 2 groups. At 6 months, fewer adjunct patients had CMO (42.7%) or a foveal thickness of >300 μm (47.6%) compared with controls (67.2% and 67.7%, respectively, P = 0.004, P = 0.023). Conclusions A slow-release dexamethasone implant did not improve the primary anatomic success rate in eyes undergoing vitrectomy surgery with silicone oil for PVR. Further clinical trials are indicated to improve anatomic and visual outcomes in these eyes, but this study suggests that there is a greater reduction in CMO observed at 6 months in vitrectomized eyes treated with slow-release dexamethasone

Characteristics and vitreoretinal management of retinal detachment in eyes with Boston keratoprosthesis.

PURPOSE: To review the incidence and features of vitreoretinal complications of a permanent Boston keratoprosthesis and to report the use and outcomes of 23-gauge vitrectomy to manage vitreoretinal pathology. DESIGN: Retrospective non-comparative, interventional case series. SUBJECT, PARTICIPANTS: 27 eyes of 27 patients managed with a Boston keratoprosthesis at Moorfields Eye Hospital over a 3-year period. METHODS: All eyes that underwent pars plana vitrectomy (PPV) and had at least 6 months follow-up were analysed with a specific focus on the anatomical and histological characteristics of retinal detachment and outcomes of surgery. MAIN OUTCOME MEASURES: Anatomical success and characteristics of retinal detachment over the follow-up period. RESULTS: 27 patients underwent Boston keratoprosthesis implantation over the study period. Of these, six (22%) required PPV for retinal detachment which demonstrated a specific pattern of serous elevation with subsequent severe anterior proliferative vitreoretinopathy (PVR). The mean follow-up period was 9 months (range 6-14 months). At final follow-up, visual acuity ranged from perception of light to 6/18, and five of six cases had attached retinae under the silicone oil. Histological analysis of a subretinal membrane demonstrated a predominantly glial/retinal pigment epithelium fibrocellular tissue, consistent with PVR. CONCLUSIONS: The study showed that retinal detachment complicated by PVR, as demonstrated by the clinical and histological characteristics of this condition, is common in patients undergoing Boston keratoprosthesis. We also showed that 23-gauge vitrectomy can be effectively performed in patients with a permanent prosthesis. Visual acuity often remains poor, despite successful anatomical results

A randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery for open globe trauma – the ASCOT study

Background: Eyes sustaining open globe trauma are at high risk of severe visual impairment. Proliferative vitreoretinopathy is the most common cause of retinal detachment and visual loss in eyes with open globe trauma. There is evidence from experimental studies and pilot clinical trials that the use of adjunctive steroid medication triamcinolone acetonide can reduce the incidence of proliferative vitreoretinopathy and improve outcomes of surgery for open globe trauma. Objective: The Adjunctive Steroid Combination in Ocular Trauma or ASCOT study aimed to investigate the clinical effectiveness of adjunctive triamcinolone acetonide given at the time of vitreoretinal surgery for open globe trauma. Design: A phase 3 multicentre double-masked randomised controlled trial randomising patients undergoing vitrectomy following open globe trauma to either adjunctive triamcinolone acetonide or standard care. Setting: Hospital vitreoretinal surgical services dealing with open globe trauma. Participants: Patients undergoing vitrectomy surgery who had sustained open globe trauma. Interventions: Triamcinolone acetonide 4 mg/0.1 ml into the vitreous cavity and 40 mg/1 ml sub-Tenon’s or standard vitreoretinal surgery and postoperative care. Main outcome measures: The primary outcome was the proportion of patients with at least 10 letters of improvement in corrected visual acuity at six months. Secondary outcomes included retinal detachment secondary to proliferative vitreoretinopathy, retinal reattachment, macula reattachment, tractional retinal detachment, number of operations, hypotony, elevated intraocular pressure and quality of life. Health-related quality of life was assessed using the EuroQol Five Domain and Visual Function Questionnaire 25 questionnaires.Results: A total of 280 patients were randomised; 129 were analysed from the control group and 130 from the treatment group. The treatment group appeared, by chance, to have more severe pathology on presentation. The primary outcome (improvement in visual acuity) and principal secondary outcome (change in visual acuity) did not demonstrate any treatment benefit for triamcinolone acetonide. The proportion of patients with improvement in visual acuity was 47% for triamcinolone acetonide and 43% for standard care (odds ratio 1.03, 95% confidence interval 0.61 to 1.75, p = 0.908); the baseline adjusted mean difference in the six-month change in visual acuity was –2.65 (95% confidence interval –9.22 to 3.92, p = 0.430) for triamcinolone acetonide relative to control. Similarly, the secondary outcome measures failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal reattachment and stable macular retinal reattachment, outcomes for the treatment group were significantly worse for triamcinolone acetonide at the 5% level (respectively, odds ratio 0.59, 95% confidence interval 0.36 to 0.99, p = 0.044 and odds ratio 0.59, 95% confidence interval 0.35 to 0.98, p = 0.041) compared with control in favour of control. The cost of the intervention was £132 per patient. Health economics outcome measures (Early Treatment Diabetic Retinopathy Study, Visual Function Questionnaire 25 and EuroQol Five Dimensions) did not demonstrate any significant difference in quality-adjusted life-years. Conclusions: The use of combined intraocular and sub-Tenon’s capsule triamcinolone acetonide is not recommended as an adjunct to vitrectomy surgery for intraocular trauma. Secondary outcome measures are suggestive of a negative effect of the adjunct, although the treatment group appeared to have more severe pathology on presentation

A Study of the Natural History of Vitreomacular Traction Syndrome by OCT

PURPOSE: To examine the natural history of vitreomacular traction syndrome (VMTS) in the absence of other ocular comorbidities. DESIGN: Retrospective clinical case series. PARTICIPANTS: A total of 183 eyes of 159 patients diagnosed with VMTS with no other ocular comorbidity. METHODS: Patients with VMTS were identified from an OCT database at Moorfields Eye Hospital, London. Sequential OCT scans and patient notes were reviewed over a minimum period of 6 months. Data collected included patient demographics, best-corrected visual acuity, and OCT features of vitreomacular adhesion. Contingency tests and binary logistic modeling were used to identify baseline predictors of stability and progression. MAIN OUTCOME MEASURES: The rates of spontaneous resolution (defined by release of traction), progression to full-thickness macular hole, and surgical intervention were analyzed. RESULTS: Presenting visual acuity was 0.3±0.3 logMAR units. The mean length of follow-up was 17.4±12.1 months. During this period, VMTS persisted in 60% and resolved in 20% (occurring on average at 15 months). Of the remainder, 12% developed a macular hole and 8% elected to proceed with surgery for symptoms. Focal adhesion <1500 μm was present in 87%. A premacular membrane with macular pucker (PMM) was present in 20%. With persistent VMTS, vision and central foveal thickness remained unchanged. The relative risk of resolution increased in those cases with better presenting visual acuities, lesser foveal thicknesses, and no associated PMMs; vision significantly improved in those cases with resolution. CONCLUSIONS: VMTS persists in the majority of patients but despite this, visual acuities did not deteriorate significantly over the study period unless patients developed a full-thickness macular hole or required surgical intervention for symptoms. Resolution spontaneously occurred in 20%, with an improvement in vision

The effect of a preoperative subconjuntival injection of dexamethasone on blood–retinal barrier breakdown following scleral buckling retinal detachment surgery: a prospective randomized placebo-controlled double blind clinical trial

textabstractBackground: Blood-retinal barrier breakdown secondary to retinal detachment and retinal detachment repair is a factor in the pathogenesis of proliferative vitreoretinopathy (PVR). We wished to investigate whether an estimated 700 to 1000 ng/ml subretinal dexamethasone concentration at the time of surgery would decrease the blood-retinal barrier breakdown postoperatively. Methods: Prospective, placebo-controlled, double blind clinical trial. In 34 patients with rhegmatogenous retinal detachment scheduled for conventional scleral buckling retinal detachment surgery, a subconjunctival injection of 0.5 ml dexamethasone diphosphate (10 mg) or 0.5 ml placebo was given 5-6 hours before surgery. Differences in laser flare photometry (KOWA) measurements taken 1, 3 and 6 weeks after randomisation between dexamethasone and placebo were analysed using mixed model ANOVA, while correcting for the preoperative flare measurement. Results: Six patients did not complete the study, one because of recurrent detachment within 1 week, and five because they missed their postoperative laser flare visits. The use of dexamethasone resulted in a statistically significant decrease in laser flare measurements at the 1-week postoperative visit. Conclusion: The use of a preoperative subconjunctival injection of dexamethasone decreased 1-week postoperative blood-retina barrier breakdown in patients undergoing conventional scleral buckling retinal detachment surgery. This steroid priming could be useful as a part of a peri-operative regime that would aim at decreasing the incidence of PVR