Retinal damage extends beyond the border of the detached retina in fovea-on retinal detachment.

PURPOSE: The aim of this study was to investigate the preoperative and postoperative change in retinal sensitivity in relation to the distance to the retinal detachment (RD) in patients with fovea-on RD. METHODS: We prospectively evaluated 13 patients with fovea-on RD and a healthy control eye. Preoperatively, OCT scans of the RD border and the macula were obtained. The RD border was highlighted on the SLO image. Microperimetry was used to assess the retinal sensitivity at the macula, the RD border and the retina around the RD border. At 6 weeks, 3 and 6 months postoperatively, follow-up examinations of OCT and microperimetry were performed in the study eye. Microperimetry was performed once in control eyes. Microperimetry data were overlaid on the SLO image. The shortest distance to the RD border was calculated for each sensitivity measurement. The change in retinal sensitivity was calculated as control-study. The relation between the change in retinal sensitivity and the distance to the RD border was assessed using a locally weighted scatterplot smoothing curve. RESULTS: Preoperatively, the greatest loss in retinal sensitivity was 21 dB at 3° inside the RD which decreased linearly, through the RD border, and reached a plateau of 2 dB at 4°. For 6 weeks and 3 months postoperatively, the greatest retinal sensitivity loss remained at 3° inside the RD but was 4 dB and sensitivity loss decreased linearly to a plateau of 0 dB at 5° outside the RD. At 6 months postoperatively, the greatest sensitivity loss was 2 dB at 3° inside the RD, and decreased linearly to a plateau of 0 dB at 2° outside the RD. CONCLUSIONS: Retinal damage extends beyond the detached retina. Retinal sensitivity loss of the attached retina decreased drastically as the distance to the RD increased. Postoperative recovery occurred for both attached and detached retina.

Smaller Foveal Avascular Zone in Deep Capillary Plexus Is Associated with Better Visual Acuity in Patients after Macula-off Retinal Detachment Surgery.

Purpose: To associate the change in the foveal avascular zone (FAZ) and vessel density (VD) with final best corrected visual acuity (BCVA) in eyes after macula-off rhegmatogenous retinal detachment surgery, and to investigate the evolution of FAZ and VD during 12 months of follow-up. Methods: We prospectively evaluated 47 patients with macula-off rhegmatogenous retinal detachment and healthy fellow eyes. At 1.5, 3.0, 6.0, and 12.0 months postoperatively, optical coherence tomography angiography scans were obtained from both eyes on a 3.0 × 3.0 mm macula-centered grid. En face images of the superficial vascular plexus, intermediate capillary plexus and deep capillary plexus were used to quantify FAZ and VD. BCVA was assessed with ETDRS-charts (logarithm of the minimal angle of resolution).At 12 months postoperatively, the association between the change in optical coherence tomography angiography parameters and visual function in study eyes was evaluated using the Spearman correlation coefficient. We calculated the BCVA difference and the percentage difference of FAZ and VD between the study and control eye. The evolution of FAZ and VD was investigated with linear mixed-effects models with nested random effects (eyes nested within patients). Results: At 12 months postoperatively, FAZ difference of the deep capillary plexus and BCVA difference were correlated (P = 0.0004, rs = 0.5). Furthermore, there was no evidence that FAZ and VD changed during follow-up. Conclusions: Although FAZ and VD remained stable during 12 months after surgery for macula-off rhegmatogenous retinal detachment, a smaller FAZ in the deep capillary plexus is associated with better BCVA. Translational relevance: Reduction in FAZ area may be caused by angiogenesis to counteract ischemia, therefore therapeutic stimulation of angiogenesis could be beneficial to visual recovery.

Visual Acuity Inadequately Reflects Vision-Related Quality of Life in Patients After Macula-Off Retinal Detachment Surgery.

Purpose: To determine the impact of postoperative visual function on the vision-related quality of life (VRQoL) in patients after anatomically successful surgery for macula-off rhegmatogenous retinal detachment (RRD) and to propose a classification to grade the extent of macular detachment using preoperative optical coherence tomography (OCT) scans. Methods: This prospective study evaluated 48 patients. At 12 months after surgery, visual function assessments were as follows: metamorphopsia (M-CHARTS), aniseikonia (New Aniseikonia Test), best corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS]), low contrast BCVA (10% ETDRS), color vision (Hardy Rand Rittler), and stereopsis (Titmus Fly). VRQoL was assessed by the National Eye Institute Visual Functioning Questionnaire-25 (NEIVFQ-25). Associations between visual function parameters and NEIVFQ-25 scores were evaluated. Preoperative OCT-scans were classified into six stages according to the extent of macular detachment based on an ETDRS-grid: incomplete perifoveal detachment (1), incomplete parafoveal detachment (2), incomplete foveal detachment (3), complete foveal detachment (4), complete parafoveal detachment (5), and complete perifoveal detachment (6). Results: General vision and driving were the lowest scoring categories. General vision had the strongest correlation with low contrast BCVA (r = -0.41, P = 0.002), while driving had the strongest correlation with stereopsis (r = -0.39, P = 0.008). All macular detachments were graded stage 3 or beyond. Patients with stage 3 macular detachments had the highest visual function values compared to the other stages. The highest percentage of patients with metamorphopsia, aniseikonia and BCVA>0.1 logMAR was found in stages 5 and 6. Conclusions: Macula-off RRD particularly affects general vision and driving. The extent of macular detachment is a potential predictor for visual function and can be graded using the proposed classification.

STRICT POSTURING WITH OR WITHOUT BILATERAL PATCHING FOR POSTERIOR VITREOUS DETACHMENT-RELATED VITREOUS HEMORRHAGE.

PURPOSE: To determine whether bilateral patching with posturing is superior to posturing alone in visualizing the superior retina in suspected posterior vitreous detachment (PVD)-related vitreous hemorrhage (VH). METHODS: Prospective randomized controlled trial: 80 patients with fundus-obscuring VH due to suspected retinal tear were randomized to strict posturing and bilateral patching overnight (Treatment A, 40 patients) or posturing (Treatment B, 40 patients). PRIMARY OUTCOME: Visualization of ≥4 clock hours superior retina. SECONDARY OUTCOME MEASURES: laser treatment, vitrectomy rate, and retinal detachment within 12 months. RESULTS: Intention-to-treat analysis: In 38/40 (95%) with Treatment A and 32/40 (80%) with Treatment B, the confirmed diagnosis was PVD-related VH. Visibility of the superior retina for all patients: 29/40 (73%) after Treatment A and 21/40 (53%) after Treatment B (P = 0.07). Subgroup analysis for confirmed PVD-related VH; visibility of the superior retina: 29/38 (76%) after Treatment A and 15/32 (47%) after Treatment B (P = 0.01). In subgroup analysis, vitrectomy rate within 12 months was 61% (Treatment A) and 53% (Treatment B) (P = 0.63). Retinal detachment: eight patients after each treatment. CONCLUSION: In patients with suspected PVD-related VH, overnight bilateral patching was not superior to posturing alone in superior retina visualization, but in a post-hoc analysis of patients with confirmed PVD-related VH, bilateral patching was superior.

Postoperative aqueous humour flare as a surrogate marker for proliferative vitreoretinopathy development.

PURPOSE: As some surgical procedures have been shown to increase postoperative flare values and thus contribute to blood-ocular barrier breakdown, retinal reattachment surgery might influence the risk of developing proliferative vitreoretinopathy (PVR). Therefore, we investigated whether postoperative aqueous flare values are a surrogate marker for the development of postoperative PVR. METHODS: We prospectively included 195 patients with primary rhegmatogenous retinal detachment (RRD) and measured aqueous laser flare preoperatively, and at 2 and 6 weeks postoperatively. Postoperative PVR was defined as reoperation for redetachment due to PVR membranes, within 6 months of initial surgery. Logistic regression and receiver operating characteristic (ROC) analysis determined whether higher postoperative flare values were associated with an increased risk of developing PVR later on. RESULTS: Reoperation for postoperative PVR was needed in 12 (6.2%) patients; in 18 (9.2%), reoperation was not related to PVR. The median flare value for patients who would develop PVR was significantly higher than that of patients who would not develop PVR, both at 2 weeks (p = 0.001) and 6 weeks (p < 0.001) postoperatively. Logistic regression analyses showed that a higher flare value significantly increased the odds of developing PVR, either at 2 weeks [odds ratio (OR) 1.027; 95% CI: 1.010-1.044] or 6 weeks (OR 1.076; 95% CI: 1.038-1.115). CONCLUSION: Flare values both at 2 and 6 weeks postoperatively seem a good surrogate marker in terms of sensitivity and specificity for the development of postoperative PVR but have only a modest positive predictive value. The 2-week value would be more useful in terms of early recognition of high-risk patients and hence give the possibility to better study effects of treatment methods.

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.

Corneal endothelial cell density after vitrectomy with silicone oil for complex retinal detachments.

PURPOSE: To evaluate the endothelial cell density changes in eyes with silicone oil tamponade after vitrectomy for complex rhegmatogenous retinal detachment. METHODS: A prospective controlled study with 81 eyes with complex rhegmatogenous retinal detachment undergoing vitrectomy and silicone oil tamponade. Fellow eyes that fulfilled specific inclusion criteria served as controls. Endothelial cell density (in cells per square millimeter), coefficient of variance (standard deviation per mean cell area × 100), percentage of hexagonal cells, and corneal thickness were documented preoperatively and compared with values obtained at 3, 6, and 12 months postoperatively. For the purpose of the study analysis, all study eyes were divided into 5 groups, according to their lens status during the follow-up. RESULTS: High endothelial cell density loss was found in Group 3, (eyes that underwent an additional phacoemulsification procedure) and Group 4 (eyes that underwent lens and/or intraocular lens removal during the follow-up) at 12 months with a mean cell loss of 19% and 39%, respectively (P < 0.001). CONCLUSION: An intact natural or artificial lens-iris diaphragm may provide a protective barrier against corneal endothelial cell damage from long-term silicone oil tamponade.

A new epidemiological aid in deciding whether to continue or stop a treatment.

PURPOSE: To present a new epidemiological method relying on randomized controlled clinical trial (RCT) data to assess whether a treatment was effective, aiding in the decision to continue or stop the treatment in clinical patients. METHODS: A cutoff point is calculated in the change of a continuous outcome for which a proportion of treated patients clearly achieved a change better than this cutoff point as a result of the treatment. This cutoff point can then be applied to individual patients during routine therapy. The method was applied to reports of the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) trial, which included patients with AMD treated with monthly intravitreal injections of ranibizumab, and to reports of trials involving patients with high IOP, macular edema, and convergence insufficiency. RESULTS: The cutoff point in the change in visual acuity (number of letters), above which a proportion of patients clearly benefited due to ranibizumab treatment, was -5.0 at 24 months follow-up. The proportion of treated patients who ended above this cutoff point due to the treatment was 60%. The cutoff point varies with time of follow-up and by subgroup. CONCLUSIONS: Contrary to common interpretation, no change, or a limited decline, in the outcome (visual acuity) can still imply that the patients are better off with the treatment than with no treatment. Stopping the treatment above the cutoff point may not be appropriate since it was effective in at least a proportion of patients. This method applies to a broad range of scales and conditions. (ClinicalTrials.gov number, NCT00056836.).

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.

Diplopia was not predictable and not associated with buckle position after scleral buckling surgery for retinal detachment.

PURPOSE: The possibility of postoperative binocular diplopia is seen as an important drawback of conventional scleral buckling surgery for rhegmatogenous retinal detachment. The goal of this study was to evaluate the occurrence and pattern of binocular diplopia after scleral buckle procedures in patients with rhegmatogenous retinal detachment. METHODS: In a retrospective study of 1,030 patients with primary rhegmatogenous retinal detachment who were treated by scleral buckle surgery between January 2001 and July 2008, the postoperative occurrence of binocular diplopia was retrieved from the medical charts. RESULTS: Secondary strabismus developed in 39 subjects (3.8%) after scleral buckle surgery during a mean follow-up of 6.4 ± 6.3 months. Twenty-eight patients (2.7%) developed strabismus because of a mechanical restriction of one of the muscles. No association was found between the position of the buckle, that is, the muscle affected, and the incidence of diplopia. A moderate significant association was found when two muscles were affected with a higher incidence of diplopia. This was, however, not found for three or more muscles. In 28 of 39 patients, binocular single vision was restored at the end of the follow-up period. In the majority, this was accomplished with conventional prism treatment. CONCLUSION: Strabismus caused by a restriction of the muscles in scleral buckle surgery was not predictable based upon the buckle position. Patients with a minimal restriction of the muscles after scleral buckle surgery can often be well treated with prisms.

Antiangiogenic isoforms of vascular endothelial growth factor predominate in subretinal fluid of patients with rhegmatogenous retinal detachment and proliferative vitreoretinopathy.

BACKGROUND: In proliferative vitreoretinopathy (PVR), a nonangiogenic eye disease that is characterized by the formation of mainly avascular membranes, vascular endothelial growth factor (VEGF) levels are found to be upregulated. Recently, it was discovered that VEGF is alternatively spliced to form the angiogenic (VEGF xxx) and antiangiogenic (VEGF xxx b) family of isoforms. Previous studies on expression of VEGF in PVR samples have not distinguished between the two families of isoforms. METHODS: We measured total VEGF and VEGF xxx b levels in subretinal fluid of patients with PVR (n = 10) and in patients with uncomplicated rhegmatogenous retinal detachment (n = 27) using enzyme-linked immunosorbent assay. RESULTS: : We found total VEGF levels to be 2- to 3-fold elevated in the PVR group as compared with the rhegmatogenous retinal detachment group (P = 0.047). Antiangiogenic VEGF xxx b isoforms predominated (>60% of total VEGF) in the majority of rhegmatogenous retinal detachment and PVR samples investigated, although a wide variability of isoform ratios was observed within both groups. CONCLUSION: The absence of an increased ratio of VEGF xxx to VEGF xxx b in patients with PVR as compared with patients with uncomplicated rhegmatogenous retinal detachment may explain a lack of blood vessels in PVR membranes. Elevated VEGF levels indicate that this cytokine may play a role in the pathogenesis of PVR that is not related to angiogenesis.

Adipokine levels in subretinal fluid from patients with rhegmatogenous retinal detachment.

Adipokines have recently emerged as a novel group of mediators with important roles in inflammatory and immune responses and in the process of wound healing. This study investigated the involvement of several adipokines in the future development of proliferative vitreoretinopathy (PVR) following reattachment surgery for rhegmatogenous retinal detachment (RRD). A multiplex immunoassay was used to measure 6 different adipokines in 75 subretinal fluid samples collected during reattachment surgery for primary RRD. Twenty-one patients who developed a redetachment due to postoperative PVR after scleral buckling surgery (PVR group) were compared with age-, sex-, and storage-time-matched RRD samples from 54 patients with an uncomplicated postoperative course (RRD group). Levels of adiponectin (P = 0.006), cathepsin S (P = 0.001), and leptin (P = 0.041) were significantly elevated in the PVR group as compared to the RRD group. Levels of tissue inhibitor of metalloproteinase (TIMP)-1 were significantly lower in the PVR group than in the RRD group (P = 0.044). After correction for diabetes, body mass index (BMI), macular involvement, and preoperative PVR, the association between postoperative PVR development and adiponectin, cathepsin S, and TIMP-1 remained statistically significant (P < 0.05), whereas the significant correlation between PVR and elevated leptin levels was lost (P = 0.068). There were no significant differences in levels of chemerin (P = 0.351) and adipsin (P = 0.915). Of all adipokines investigated, multivariate logistic regression analysis showed that adiponectin was the exclusive predictor of the development of postoperative PVR after scleral buckling surgery (P = 0.003). Our findings indicate that, at the time of surgery for primary RRD, an altered expression of certain adipokines is associated with the future development of postoperative PVR.

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-1ß, 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.

Persistent subfoveal fluid and increased preoperative foveal thickness impair visual outcome after macula-off retinal detachment repair.

PURPOSE: To investigate the influence of subfoveal fluid and foveal thickness on visual outcome in patients who underwent reattachment surgery for rhegmatogenous retinal detachment (RRD). METHODS: This prospective study included 53 patients who were undergoing successful scleral buckling surgery for primary RRD. A thorough ophthalmologic examination including best-corrected visual acuity, slit-lamp biomicroscopy, binocular indirect ophthalmoscopy, and optical coherence tomography scanning was performed preoperatively and during all subsequent follow-up visits at 1, 3, 6, 9, 12, and 24 months postoperatively. RESULTS: Preoperative foveal thickness was significantly higher in the macula-off group (n = 38) compared with the macula-on group (n = 15) (P < 0.0001), whereas postoperative measurements were normal in both the groups. Linear mixed-model analysis revealed that persistent subfoveal fluid (P = 0.0004) was an independent predictor of a worse visual outcome after scleral buckling surgery for primary macula-off RRD, although the effect on visual outcome was small (0.1 logarithm of the minimal angle of resolution units). Moreover, increased preoperative foveal thickness was associated with a worse visual prognosis in macula-off RRD (P = 0.010). CONCLUSION: Persistent subfoveal fluid and increased preoperative foveal thickness were associated with a worse visual prognosis in macula-off RRD patients, albeit the effect of persistent subfoveal fluid was small and temporary.