Ellen C. La Heij

Vitrectomy results in diabetic macular oedema without evident vitreomacular traction

Abstract.Purpose: To determine the effectiveness of vitrectomy in eyes with diabetic macular oedema without evident traction from a thickened vitreous membrane. Methods: Twenty-one consecutive eyes from 19 patients with diabetic macular oedema that had undergone vitrectomy were analysed retrospectively. All eyes had an attached posterior hyaloid membrane in the macular region, but without thickening and without evident traction on the macula. A standard pars plana vitrectomy with the creation of a posterior vitreous detachment was performed. Results: Median duration of macular oedema at the time of vitrectomy was approximately 11.0 months (range 2–36 months). The median preoperative best-corrected visual acuity of 0.08 (range hand motions/0.003 to 0.4), improved by 5 lines to a median final postoperative best-corrected visual acuity of 0.25 (range 0.025–0.5) (P=0.001). Seven eyes without preoperative macular photocoagulation had a median visual acuity improvement of 77%, range 32–400%, while 12 eyes with preoperative macular laser treatment had a median visual acuity improvement of 14.8%, range 0–66.1% (P=0.02, CI 95%, after multivariate regression analysis). In all 21 eyes, macular oedema was no longer visible on microscopic examination after a median period of 3.0 months (range 1–9 months) after vitrectomy. Conclusions: In eyes with diabetic macular oedema without evident macular traction from a thickened vitreous membrane, vitrectomy resulted in the resolution of macular oedema, with an improvement in visual acuity in the majority of cases. Eyes without preoperative macular photocoagulation had a significantly higher percentage visual improvement than eyes without preoperative macular laser treatment. A randomised controlled prospective trial of primary vitrectomy versus macular photocoagulation is needed to determine the role of vitrectomy as treatment modality for diabetic macular oedema.

A Systematic Review Of The Adverse Events Of Intravitreal Anti-vascular Endothelial Growth Factor Injections

Background: Intravitreal ranibizumab and pegaptanib are registered for neovascular age-related macular degeneration. No formal safety study has been conducted for intravitreal bevacizumab. These anti-vascular endothelial growth factor (anti-VEGF) drugs are being used on a large scale in daily practice for different ocular diseases. The objective of the present study was to systematically assess and compare the incidences of adverse events of anti-VEGFs. Methods: A systematic search was conducted in April 2009 with no date restrictions in PubMed, Embase, Toxline, and the Cochrane library. We used the terms pegaptanib, bevacizumab, ranibizumab, intravitreal, and specific and general terms for adverse events. Studies describing adverse events after anti-VEGF injections and the official safety data were included. Results: Two hundred and seventy-eight articles were included, and the incidences of adverse events were calculated separately for effect, safety, and specific side effect studies. The incidences of serious ocular and nonocular adverse events were approximately below 1 per 100 injections for intravitreal bevacizumab, intravitreal ranibizumab, and intravitreal pegaptanib. Most mild ocular adverse events were below 5 per 100 injections. Conclusion: The reported rates of serious adverse events were low after anti-VEGF injections. There is no sufficient evidence to conclude that there is a difference in incidences between the anti-VEGFs.

Interleukin and growth factor levels in subretinal fluid in rhegmatogenous retinal detachment: a case-control study.

Background Rhegmatogenous retinal detachment (RRD) is a major cause of visual loss in developed countries. Proliferative vitreoretinopathy (PVR), an eye-sight threatening complication of RRD surgery, resembles a wound-healing process with inflammation, scar tissue formation, and membrane contraction. This study was performed to determine the possible involvement of a wide range of cytokines in the future development of PVR, and to identify predictors of PVR and visual outcome. Methodology A multiplex immunoassay was used for the simultaneous detection of 29 different cytokines in subretinal fluid samples from patients with primary RRD. Of 306 samples that were collected and stored in our BioBank between 2001 and 2008, 21 samples from patients who developed postoperative PVR were compared with 54 age-, sex-, and storage-time–matched RRD control patients who had an uncomplicated postoperative course during the overall follow-up period. Findings Levels of IL-1α, IL-2, IL-3, IL-6, VEGF, and ICAM-1 were significantly higher (P<0.05) in patients who developed postoperative PVR after reattachment surgery than in patients with an uncomplicated postoperative course, whereas levels of IL-1β, IL-4, IL-5, IL-7, IL-9, IL-10, IL-11, IL-12p70, IL-13, IL-15, IL-17, IL-18, IL-21, IL-22, IL-23, IL-25, IL-33, TNF-α, IFN-γ, IGF-1, bFGF, HGF, and NGF were not (P>0.05). Multivariate logistic regression analysis revealed that IL-3 (P = 0.001), IL-6 (P = 0.047), ICAM-1 (P = 0.010), and preoperative visual acuity (P = 0.026) were independent predictors of postoperative PVR. Linear regression analysis showed that ICAM-1 (P = 0.005) and preoperative logMAR visual acuity (P = 0.001) were predictive of final visual outcome after primary RRD repair. Conclusions/Significance Our findings indicate that after RRD onset an exaggerated response of certain cytokines may predispose to PVR. Sampling at a time close to the onset of primary RRD may thus provide clues as to which biological events may initiate the development of PVR and, most importantly, may provide a means for therapeutic control.

Levels of basic fibroblast growth factor, glutamine synthetase, and interleukin-6 in subretinal fluid from patients with retinal detachment.

PURPOSE To investigate the presence of basic fibroblast growth factor, glutamine synthetase activity, and interleukin-6 in subretinal fluid from patients with retinal detachment. METHODS In a prospective study we measured basic fibroblast growth factor, glutamine synthetase activity, interleukin-6, and total protein in subretinal fluid samples from 96 eyes from 94 consecutive patients with a retinal detachment corrected by a conventional scleral buckling operation in our clinical practice. As controls, vitreous fluid samples from eyes with a macular hole (n = 6) or pucker (n = 11) were used. Laboratory data of the patient group were compared with the control group and correlated with various clinical data. RESULTS Levels (median, range) of basic fibroblast growth factor, glutamine synthetase activity, interleukin-6, and total protein were significantly higher in patients than in controls (P <.0001). An increased level of glutamine synthetase and total protein correlated with a longer duration of the retinal detachment (r =.4, P =.002, and r =.34, P =.001, respectively). Interleukin-6 and basic fibroblast growth factor levels did not correlate with the duration of the detachment. After multivariate logistic regression analysis, no significant relation was found between any of the tested subretinal proteins and a low visual outcome or redetachment. CONCLUSIONS We found increased levels of basic fibroblast growth factor and glutamine synthetase in subretinal fluid from patients with retinal detachment. Basic fibroblast growth factor and glutamine synthetase may play a role in the pathogenesis and recovery after retinal detachment. The questions of whether the increased levels of basic fibroblast growth factor and glutamine synthetase result from leakage of dying glia cells (including Müller cells) and neurons and if basic fibroblast growth factor is actively produced to protect the photoreceptor cells need further research.

Incidence of redetachment 6 months after scleral buckling surgery

Purpose:  The preoperative and intraoperative clinical variables associated with redetachment and/or a poor visual outcome following scleral buckling (SB) surgery for rhegmatogenous retinal detachment (RRD) have mainly been studied after a short follow‐up. This study aimed to analyse long‐term effects by following patients for at least 6 months.

Anterior Chamber Depth Is Significantly Decreased after Scleral Buckling Surgery

OBJECTIVE Myopic patients have an increased risk for the development of a rhegmatogenous retinal detachment (RRD). Currently, myopic patients have the choice to undergo correction of their refractive error by the implantation of a phakic intraocular lens (pIOL). After pIOL implantation, progressive endothelial cell loss may result if the anterior chamber is too shallow. Because scleral buckling (SB) surgery for treatment of an RRD may in itself result in a decreased anterior chamber depth (ACD), this may become an important issue not only for the retinal surgeon who is faced with a patient who has both an RRD and a pIOL, but also for the refractive surgeon who should consider the potential problems of the implantation of pIOL in an eye that has previously undergone SB surgery. The goal of this study was to evaluate how long changes in ACD persist after SB procedures in patients with RRD. DESIGN Prospective case series. PARTICIPANTS Thirty-eight eyes with a primary RRD treated by SB using an encircling element and a radial or segmental buckle; 31 fellow eyes served as controls. METHODS Anterior chamber depth (in the horizontal meridian) and axial length were measured preoperatively and at 1 week and 1, 3, 6, 9, and 12 months postoperatively with an anterior optical coherence tomography method and an IOLMaster (Carl Zeiss Meditec, Jena, Germany), respectively. MAIN OUTCOME MEASURES In all 38 eyes, ACD was significantly reduced compared with preoperative levels up to 9 months after SB surgery. RESULTS Anterior chamber depth returned to normal at 1 year after surgery. Axial length was significantly enlarged during the whole follow-up period. No significant differences were found between the use of radial or segmental buckles. CONCLUSIONS Anterior chamber depth may remain decreased after SB for a longer time period than previously reported. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.

Prediction of Proliferative Vitreoretinopathy after Retinal Detachment Surgery: Potential of Biomarker Profiling

PURPOSE To investigate the potential of a combined assessment of clinical risk factors and biomarker profiling in the prediction of proliferative vitreoretinopathy (PVR) after retinal detachment surgery. DESIGN Retrospective case-control study. METHODS Multiplex bead-based immunoassays were used for the simultaneous measurement of 50 biomarkers in subretinal fluid samples obtained from patients who underwent scleral buckling surgery for primary rhegmatogenous retinal detachment (RRD). Of 306 samples that were collected and stored in our BioBank, we selected 21 samples from patients in whom a redetachment developed as a result of PVR within 3 months after reattachment surgery for primary RRD (PVR group). These were compared with age-, sex-, and storage time-matched RRD samples from 54 patients with an uncomplicated postoperative course after primary RRD repair (RRD group). RESULTS Preoperative PVR was the only clinical variable that was an independent predictor of postoperative PVR development (P = .035) and resulted in an area under the receiver operating characteristic curve of 0.67 (95% confidence interval, 0.51 to 0.83). The addition of the biomarkers chemokine (C-C motif) ligand 22, interleukin-3, and macrophage migration inhibitory factor improved the model significantly (P < .001) and resulted in an area under the receiver operating characteristic curve of 0.93 (95% confidence interval, 0.82 to 1.04). A sensitivity of 94.1% and a specificity of 94.2% were reached, using a cutoff value of 5%. CONCLUSIONS In combination with preoperative PVR grade, the measurement of a single biomarker or a small multibiomarker panel shows great potential and may predict postoperative PVR development after primary RRD in a highly sensitive and specific manner.

Impact Of Duration Of Macula-off Retinal Detachment On Visual Outcome: A Systematic Review and Meta-analysis of Literature

Purpose: To systematically review the influence of the lag time between macula-off retinal detachment and surgical intervention on postoperative visual acuity as main outcome measure. Methods: Systematic review and meta-analysis of articles published from 1995 to October 2013 of patients with macula-off retinal detachment and treated with scleral buckling or pars plana vitrectomy. Eligible data were pooled in a meta-analysis, analyzing the odds ratio between different durations of ⩽3, ⩽4, ⩽7, and ⩽10 days, comparing a final visual acuity of ⩽0.4 logMAR with >0.4 logMAR, using a random-effects model. Last, the number needed to treat was calculated. Results: Fourteen articles were eligible, of which 9 studies contained data that were suitable for meta-analysis. Patients who were operated with scleral buckling (n = 602) within 3 days since macular detachment had a statistically significant better chance of reaching a final visual acuity of 0.4 logMAR or better compared with a longer duration of macular detachment, with an odds ratio for ⩽3 days versus 4 days to 7 days of 2.86 (95% confidence interval, 1.37–5.99) and an odds ratio for ⩽3 days versus >3 days of 3.09 (95% confidence interval, 1.56–6.12), and with a number needed to treat of 4. For pars plana vitrectomy, the limited amount of data precluded a meta-analysis with substantial results. Conclusion: This meta-analysis suggests that scleral buckling for macular detachment must preferably be performed within 3 days to optimize visual outcome.

Soluble Apoptotic Factors and Adhesion Molecules in Rhegmatogenous Retinal Detachment

PURPOSE To investigate the association between soluble apoptosis and adhesion molecules and the development of proliferative vitreoretinopathy (PVR) after reattachment surgery for rhegmatogenous retinal detachment (RRD). METHODS A multiplex immunoassay was used to measure soluble Fas (sFas), sFas ligand (sFasL), soluble intercellular adhesion molecule (sICAM)-1, and soluble vascular cell adhesion molecule (sVCAM)-1 levels in 55 subretinal fluid samples collected during scleral buckling surgery for primary RRD. Seventeen patients who developed a redetachment due to postoperative PVR after reattachment surgery (PVR group) were compared with age-, sex-, and storage-time-matched RRD samples from 38 patients with an uncomplicated postoperative course (RRD group). Ten vitreous samples from patients with macular hole and ten vitreous samples from eye bank eyes served as additional controls. RESULTS A 2- to 3-fold increase in levels of sFas, sFasL, sICAM-1, and sVCAM-1 was found in the PVR group compared with those of the RRD group (P < 0.05 for all analytes), as well as a 5- to 20-fold increase in the PVR group compared with those of additional control groups (P < 0.001 for all analytes). Significant associations (P < 0.001) were found between sFas and both sICAM-1 (r = 0.84) and sVCAM-1 (r = 0.93) and between sFasL and both sICAM-1 (r = 0.82) and sVCAM-1 (r = 0.85). In addition, sFas, sFasL, and sVCAM-1 were significantly correlated (P < 0.05) with the extent and duration of retinal detachment. CONCLUSIONS These findings indicate that an increased expression of soluble apoptosis and adhesion molecules at the time of primary retinal detachment surgery is associated with the future development of PVR.

High Subretinal Fluid Procoagulant Activity in Rhegmatogenous Retinal Detachment

PURPOSE An increased mRNA expression of genes related to blood coagulation has been demonstrated in an experimental retinal detachment model but has not yet been confirmed in human clinical specimens. Tissue factor (TF), the initiating factor of blood coagulation, may be a determinant of the extent of tissue injury after rhegmatogenous retinal detachment (RRD). This study was conducted to determine whether subretinal fluid and vitreous fluid collected from patients with RRD have a procoagulant effect. METHODS Calibrated thrombin generation (CAT) was used to investigate the thrombogenic properties of 28 subretinal fluids collected during scleral buckling surgery for RRD. Further, the thrombogenic properties of vitreous fluids from RRD (n = 12), macular pucker (n = 5), macular hole (n = 6), and proliferative diabetic retinopathy (n = 5) were compared with the properties of eye bank eyes (n = 11), which served as control specimens. The procoagulant activity of TF was determined with Western blot analysis. RESULTS The addition of subretinal fluid from all RRD patients (28/28, 100%) induced thrombin generation in normal and severely factor (F)XII-deficient plasma. Contrary to the subretinal fluid, the addition of vitreous fluids from various ocular disorders evoked very little thrombin generation in normal and severely FXII-deficient plasma (4/12, 33% RRD; 1/5, 20% macular pucker; 0/6, 0% macular hole; 0/5, 0% proliferative diabetic retinopathy; and 2/11, 18% eye bank eyes). The procoagulant activity in subretinal fluid was almost completely neutralized by antibodies against human TF. The presence of TF in subretinal fluid was confirmed by Western blot. CONCLUSIONS Subretinal fluid of patients with RRD induces high procoagulant activity, determined by measuring the level of tissue factor.