Prediction of Glaucomatous Visual Field Progression Using Baseline Clinical Data.

PURPOSE: To develop a prediction model for glaucomatous visual field progression using easily accessible baseline clinical data. PATIENTS AND METHODS: We collected baseline data of 613 consecutive patients with open-angle glaucoma from 2001 to 2003. The rate of visual field progression was calculated using the Visual Field Index (VFI) of routine follow-up examinations until 2010. Baseline data of 333 patients from 3 hospitals were used to develop a model to predict the rate of VFI progression using a linear regression analysis and univariate preselection (P<0.1) of 8 candidate predictors. The performance of the model was investigated using R, the area under the receiver-operating characteristic curve, and calibration plots. The prediction model was internally validated using bootstrapping and externally validated in 280 patients from 2 other hospitals. RESULTS: After a mean follow-up period of 5.8 years of all 613 eyes, the mean rate of VFI progression was -1.6% per year. The final model contained the following predictors: age, baseline intraocular pressure, and baseline visual field status. During model development, 10.3% of the observed variation in VFI rates was explained by the model. The area under the receiver-operating characteristic curve was 0.76 when the prediction model was used to detect a VFI rate of -3% per year or worse, which decreased to 0.71 at external validation. CONCLUSIONS: Although our prediction model could explain only a small amount of the variance in visual field progression, it may offer the possibility to identify subgroups of treated patients with high rates of visual field progression, thereby providing an opportunity to select those patients for more intensive treatment.

The long term effectiveness and cost-effectiveness of initiating treatment for ocular hypertension.

PURPOSE: To investigate the long-term health and economic consequences of direct treatment initiation in ocular hypertension patients. METHODS: A cost-effectiveness analysis with a societal perspective and a lifelong horizon was performed. The primary outcomes were the incremental quality-adjusted life years (QALYs) and costs of direct pressure-lowering treatment for ocular hypertension, compared to a strategy where treatment is postponed until conversion to glaucoma has been observed. We used a decision analytic model based on individual patient simulation to forecast disease progression and treatment decisions in both strategies in a representative heterogeneous patient population and in 18 patient subgroups stratified by initial intraocular pressure and additional risk factors for conversion. RESULTS: The incremental discounted health gain of direct treatment was 0.27 QALYs, whereas the incremental discounted costs were -€ 649 during an average lifetime of 26 years. In the simulations of patient subgroups, the model outcomes moved towards higher health gains and lower incremental costs with increasing risk of conversion in the patient population. The incremental cost-effectiveness ratio of direct treatment ranged from € 15,425 per QALY gained in the lowest-risk subgroup to dominance in the highest-risk subgroup. Probabilistic sensitivity analysis indicated that uncertainty surrounding the model input parameters did not affect the conclusions. CONCLUSION: Direct, early, pressure-lowering treatment is a dominant cost-effective treatment strategy over a strategy to start the same treatment approach later, after glaucoma has occurred for patients with ocular hypertension. Its implementation and consequences should be discussed with ophthalmologists and individual patients.

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.

Prevalence of end-of-life visual impairment in patients followed for glaucoma.

PURPOSE: To assess the prevalence of end-of-life visual impairment in patients followed for glaucoma. METHODS: Data of 122 patients followed for glaucoma who had died between July 2008 and July 2010 and who had visited the ophthalmology outpatient department of a large non-academic Dutch hospital were collected from the medical files. Sixty-one patients had open-angle glaucoma (OAG), and 61 patients were suspect for glaucoma or had ocular hypertension (OHT). Visual impairment was defined as a mean deviation value <-15 dB or a Snellen visual acuity <0.3 (20/60) of the better eye. We determined the number of patients with visual impairment on the last patient visit before death and investigated its main explanations. RESULTS: Overall, the mean age at death was 81.8 years after a mean follow-up period of 9.2 years. Seventy-three per cent of all patients had their last visit in the year preceding death. In OAG, 16 patients (26%) had an end-of-life visual impairment. In nine patients (15%), this was caused by glaucoma. Eight of them had substantial visual loss at the initial visit. Six (10%) impaired OAG cases were mainly explained by ocular comorbidity, and there was an equal contribution of comorbidity and glaucoma in one case. Five glaucoma suspects or patients with OHT (8%) were visually impaired at death and these were all caused by ocular comorbidity. CONCLUSION: The prevalence of end-of-life visual impairment is considerable in patients with OAG. Substantial visual loss at baseline is an important contributing factor. In glaucoma suspects or patients with OHT, the prevalence is lower and can be attributed to ocular comorbidity.

An evidence-based review of prognostic factors for glaucomatous visual field progression.

PURPOSE: To examine which prognostic factors are associated with glaucomatous visual field progression. DESIGN: Knowledge of prognostic factors helps clinicians to select patients at risk of glaucomatous visual field progression and intensify their treatment. METHODS: By consulting relevant databases, we identified 2733 articles published up to September 2010, of which 85 articles investigating prognostic factors for visual field progression in patients with open-angle glaucoma (OAG) were eligible. We summarized results for each factor in tables, noting the direction of the association between the prognostic factor and progression, and the accompanying P value. Four authors, working blind to the factors, independently judged the extent to which a prognostic factor was associated with glaucomatous visual field progression. If there were different associations for normal-tension glaucoma (NTG) studies, they were judged separately. Consensus was reached during group meetings. MAIN OUTCOME MEASURES: A ranking of all studied prognostic factors for glaucomatous visual field progression according to their likelihood of being prognostic. RESULTS: A total of 103 different prognostic factors were investigated in 85 articles. The following factors were clearly associated with glaucomatous visual field progression: age, disc hemorrhages (for NTG), baseline visual field loss, baseline intraocular pressure (IOP), and exfoliation syndrome. An association was unlikely for family history of glaucoma, atherosclerosis, systemic hypertension, visual acuity, sex (for NTG), systolic blood pressure, myopic refractive error (for NTG), and Raynaud's phenomenon. CONCLUSIONS: The factors we found clearly associated with progression could be used in clinical practice and for developing clinical prediction models. For many other factors, further research is necessary.

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.

The long-term outcomes of four alternative treatment strategies for primary open-angle glaucoma.

PURPOSE: To evaluate the long-term effects and costs of four treatment strategies for primary open-angle glaucoma compared to usual care. METHODS: Cost-effectiveness analyses with a lifelong horizon were made from a societal perspective. Data were generated with a patient-level model based on discrete event simulation. The model structure and parameter estimates were based on literature, particularly clinical studies on the natural course of glaucoma and the effect of treatment. We simulated heterogeneous cohorts of 3000 patients and explored the impact of uncertainty with sensitivity analyses. RESULTS: The incremental cost-effectiveness ratio (ICER) of initial treatment with a prostaglandin analogue compared with a ß-blocker was €12.931 per quality-adjusted life year (QALY) gained. A low initial target pressure (15 mmHg) resulted in 0.115 QALYs gained and €1550 saved compared to a gradual decrease from 21 to 15 mmHg upon progression. Visual field (VF) measurements every 6 rather than 12 months lead to health gains at increased costs (ICER €173,486 per QALY gained), whereas measurements every 24 months lead to health losses at reduced costs (ICER €21,516 per QALY lost). All treatment strategies were dominant over 'withholding treatment'. CONCLUSIONS: From a cost-effectiveness point of view, it seems advantageous to aim for a low intraocular pressure in all glaucoma patients. The feasibility of this strategy should therefore be investigated. Additionally, the cost-effectiveness outcomes of initiating monotherapy with a prostaglandin analogue and reducing the frequency of VF testing may be acceptable.

The influence of the assessment method on the incidence of visual field progression in glaucoma: a network meta-analysis.

PURPOSE: To study and quantify the difference in incidence of progression between methods for the assessment of glaucomatous visual field progression. METHODS: We identified 2450 articles published up to April 2009 in the following data sources: PubMed, EMBASE, and Cochrane. Ten studies covering 30 methods were included. All studies aimed to compare different methods for the assessment of glaucomatous visual field progression in the same study population. A network meta-analysis using a mixed-effects model was performed to combine within-study between-method comparisons with indirect comparisons from other studies. The summarized incidence of progression was calculated for every method, and methods were ranked according to this incidence. RESULTS: In total, methods were compared in 1040 eyes of 948 patients with glaucoma. On average, 21% of the eyes progressed. When all 30 methods were ranked, the incidence ranged from 2% to 62%. These incidences are corrected for a baseline mean deviation (MD) value of -7 decibels and a mean follow-up time of 6 years. Besides the assessment method, the incidence was only determined by the follow-up period and baseline MD value, leaving no unexplained variance in the incidence of progression. CONCLUSION: The incidence of progression varies considerably between different studies. This is mainly caused by the variety of methods used to assess progression but also by differences in follow-up time and baseline visual field loss.

Latanoprost versus timolol as first choice therapy in patients with ocular hypertension. A cost-effectiveness analysis.

PURPOSE: To determine the cost-effectiveness of ocular hypertension (OH) treatment initiated with latanoprost compared to timolol. METHODS: Two strategies for OH therapy are modelled, (1) 'starting with timolol' and (2) 'starting with latanoprost'. Therapy can be maintained or changed dependent on the achieved intraocular pressure (IOP) and side-effects. Adjustments of therapy to reach a target pressure involve monotherapy, combination therapy and laser. Four drugs are used: latanoprost, timolol, brimonidine and dorzolamide. Once the adjustments of therapy are completed, lifelong follow-up with IOP-dependent conversion to glaucoma and progression to blindness are modelled. Direct medical costs are assigned. The IOP-lowering effect of drugs is based on meta-analyses and applied by Monte Carlo simulation to a hypothetical cohort of patients with OH. The characteristics of the cohort, including the initial IOP distribution, are based on data of 1000 patients. RESULTS: The IOP decreased from 25,4 mm Hg (mean) to 16.7 (±0.017) mm Hg (strategy 1) and to 16.5 (±0.013) mm Hg (strategy 2). Costs per patient within 15 months of therapy were € 367 and € 469, respectively. Lifetime blindness and costs were 0.0334 years and € 3,514 (strategy 1) and 0.0318 years and € 4,397 (strategy 2). Incremental costs per year of vision saved for strategy (2) in comparison with strategy (1) amount to, given the uncertainties in the model, approximately € 537,000. CONCLUSION: For saving 1 year of vision, high costs are needed when OH therapy is initiated with latanoprost compared to timolol, when the cost price of latanoprost remains high.

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.

The evidence base to select a method for assessing glaucomatous visual field progression.

A large number of methods have been developed for assessing glaucomatous visual field progression, but their properties have not yet been systematically evaluated. In this systematic literature review, we summarize the evidence base for selecting a method by providing answers to ten relevant questions on the variety, validity and reproducibility of methods. In total, we found 301 different methods in 412 articles. The majority of studies (54%) used the Humphrey Field Analyzer. No data have been published about the reproducibility of methods. Although there is no gold standard to assess glaucomatous visual field progression, we found evidence on validity for 48 different methods. Some methods were less capable of distinguishing between progressive and nonprogressive patients. Choosing among twelve methods is supported by some evidence of their validity. These methods still differ in sensitivity, specificity and predictive values of test results within studies comparing several methods. In conclusion, the current evidence base is not perfect. A selection should be made from a limited number of methods, according to the clinical purpose of progression assessment. Methods that quantify the rate of visual field progression seem to be the most appropriate for guiding subsequent medical actions in individual patients. Future studies should investigate whether using one method to monitor patients is superior to another method in preventing loss of quality of life.

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.

Detection of Raman spectra in ocular drugs for potential in vivo application of Raman spectroscopy.

PURPOSE: Raman spectroscopy holds potential for the assessment of intraocular pharmacokinetics. Raman spectra of ocular drugs were acquired, to determine the drug-specific Raman signature. The ability of the Raman technique to quantify drug concentrations was also investigated. METHODS: The experimental setup was based on a High Performance Raman Module 2500 Raman module, designed for 180° "backscatter" signal detection in the wavenumber range of 400-1,800 cm(-1). Excitation source was a diode laser emitting a beam with a wavelength of 785 nm and a power of 10 mW. Laser light was focused in the sample with a long-working-distance microscope objective (25×/0.50). Samples were measured in quartz cuvettes in 10 sequential measurements, with exposure time 30 s. The total number of measured drugs was 49. To determine whether signal intensity and drug concentration correlate, 2 drugs were diluted in water and measured with 120 s exposure time at different concentrations. RESULTS: An active ingredient-specific Raman signature was detected in 4 glaucoma drugs, 6 mydriatics, 5 antibiotics, 4 anesthetics, 3 anti-inflammatory drugs, 2 types of artificial tears, and 5 other drugs. In 20 drugs, no specific Raman signature was detected. Linear correlation of drug concentration with signal intensity was high (R(2)≥0.94). CONCLUSIONS: Using low laser powers, Raman signatures for 29 commonly used ocular drugs were detected. Correlation of drug concentration with signal intensity is high, which is essential for monitoring drug concentration in ocular media. The presented results encourage the use of Raman spectroscopy to acquire detailed information on the pharmacokinetics of these ocular drugs.

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.

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.

The clinical impact of 2 different strategies for initiating therapy in patients with ocular hypertension.

PURPOSE: To assess the impact of 2 strategies for initiating therapy in ocular hypertension (OH) on drug use, intraocular pressure (IOP), and blindness caused by glaucoma. METHODS: Using a simulation model, initiating therapy with timolol (strategy 1) and with latanoprost (strategy 2) was simulated for a hypothetic cohort of ocular hypertension patients with an initial IOP distribution (data of 1000 patients). Adjustment of therapy within 15 months and a subsequent lifelong follow-up, with an IOP dependent conversion to glaucoma, were modeled. The IOP lowering effect of medication (based on a meta-analysis) was applied by Monte Carlo simulation. Therapy could be maintained or changed, depending on the achieved IOP and side effects. Four drugs (latanoprost, timolol, brimonidine, dorzolamide) were used as monotherapy or in combination. Glaucoma conversion rate was based on literature. RESULTS: Treatment goal was achieved in both strategies in 90% by monotherapy. This was 60% for patients with initial IOP's of 30 mm Hg. The originally prescribed medication was maintained in 66% (1) and in 77% (2). IOP decreased with approximately 34%, from 25.4 mm Hg (mean) to 16.7 mm Hg (1) and to 16.5 mm Hg (2) Blindness per person within 18.7 years of life expectancy was 0.0923 years (1) and 0.0870 years (2), which corresponds to approximately 1 month. The difference between strategies was 2 days spent in blindness per patient. CONCLUSIONS: The difference in clinical effects of the strategies is small. This is largely owing to the key concept of a target pressure, which underlies both strategies.