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.

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.

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.

Chemokine levels in subretinal fluid obtained during scleral buckling surgery after rhegmatogenous retinal detachment.

PURPOSE: Interleukin (IL)-6, a multifunctional cytokine with regulatory functions in wound healing, and several chemokines have been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD). The exact role of these chemokines, their correlation with IL-6 after primary RRD, and their association with the future development of PVR are not yet known. METHODS: A multiplex immunoassay was used to determine levels of 15 different chemokines and IL-6 in subretinal fluid samples obtained during scleral buckling surgery for primary RRD. Samples from patients with preoperative uveitis, preoperative trauma, or preoperative vitreous hemorrhage were excluded. Patients who developed a redetachment due to postsurgical PVR within 2.5 months (n = 21) were compared with control subjects who had an uncomplicated retinal detachment during the overall follow-up period (n = 54). Control subjects were matched for sex, age, and storage time. RESULTS: Levels of IL-6 (P = 0.001), MIF (P = 0.016), CCL2 (P = 0.041), CCL11 (P = 0.012), CCL17 (P = 0.003), CCL18 (P = 0.007), CCL19 (P < 0.001), CCL22 (P < 0.001), CXCL8 (P = 0.027), CXCL9 (P = 0.007), and CXCL10 (P = 0.002) were significantly higher in patients who developed postoperative PVR after primary RRD than in patients with uncomplicated retinal detachment. A significant positive correlation was observed between IL-6 and both CCL22 (r = 0.538; P < 0.0001) and CXCL8 (r = 0.645; P < 0.0001). CONCLUSIONS: Various chemokines and IL-6 are upregulated in patients in whom fibrotic membranes develop after primary RRD repair and may therefore be involved in the future development of postoperative PVR.

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.

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. METHODS: In a retrospective survey we evaluated the data of 436 eyes that underwent SB surgery. Postoperative data were collected at 3-month intervals. RESULTS: After a mean follow-up period of 51 months, anatomic reattachment was achieved in 76% after one SB procedure, with a final reattachment rate of 97% after additional vitreoretinal procedures. In total, 104 eyes developed redetachment during follow-up. After more than 6 and 12 months of follow-up, 32 eyes (7%) and 20 eyes (5%), respectively, developed redetachment. Multivariate regression analysis showed that recurrent redetachment and more than 7 days of visual field loss were significant predictors for a poor postoperative visual outcome at 12 months. A cumulative size of the tear of more than three disc diameters was a significant predictor of recurrent RRD. CONCLUSION: Conventional SB surgery is a reliable procedure in a selected group of eyes with primary RRD. However, in eyes with a retinal tear with a cumulative size of more than three disc diameters, a primary vitrectomy should be considered. Taking into account that 7% of eyes developed redetachment after 6 months, a longer follow-up period seems necessary to evaluate the anatomical and visual outcomes after SB surgery.

Value of preoperative phakic intraocular lens simulation using optical coherence tomography.

PURPOSE: To compare the position of the iris-fixated phakic intraocular lens (pIOL) in preoperative simulation and after implantation using anterior segment optical coherence tomography (AS-OCT). SETTING: Department of Ophthalmology, Academic Hospital Maastricht, Maastricht, The Netherlands. METHODS: In this prospective study, the morphometrics of the anterior chamber were analyzed using preoperative pIOL simulation and postoperative images assessed with AS-OCT. Patients' eyes were examined before and 6 months after pIOL implantation. The measured distances were from the center of the pIOL to the endothelium, from the edge of the pIOL to the endothelium (nasal and temporal side), and from the back of the pIOL to the crystalline lens. RESULTS: Thirty-four eyes (18 patients) were examined. All morphometric parameters showed highly significant correlations and small mean differences between preoperative and postoperative measurements. However, the distance from the nasal edge of the pIOL to the endothelium and the distance from the pIOL to the crystalline lens showed a statistically significant difference between the preoperative simulation and the actual postoperative measurements (P = .045 and P = .001, respectively). The ranges of agreement between all preoperative simulations and postoperative measurements ranged between 0.24 mm and 0.29 mm. CONCLUSIONS: Preoperative simulation was a useful additional tool in the selection of patients considering pIOL implantation and in ensuring the long-term safety of pIOLs. However, clinicians should be aware of the range between the preoperative simulation and the postoperative measurements.

Histologic evaluation of human posterior lamellar discs for femtosecond laser Descemet's stripping endothelial keratoplasty.

PURPOSE: To evaluate the histologic changes in corneal structure after femtosecond laser preparation of posterior lamellar discs, more specifically, the smoothness of the stromal bed and the accuracy of the predicted depth of the horizontal lamellar cut. MATERIALS AND METHODS: Nineteen human donor eyes unsuitable for transplantation were used. Femtosecond laser was used to prepare a horizontal lamellar cut in donor corneas at a depth of 400 microm. Transmission electron microscopy images were used to evaluate the changes in the corneal structure and to measure the damage zone. Scanning electron microscopy images were used to determine the relative depth of the horizontal lamellar cut, and the stromal bed was examined to determine the smoothness of the surface. RESULTS: Transmission electron microscopy images showed a mean damage zone of 6.8 +/- 3.1 microm, which consisted of irregularly oriented collagen fibrils and electron-dense granular material. The collagen lamellae, both anteriorly and posteriorly of the damaged zone, showed a regular parallel configuration. The relative depth of the horizontal lamellar cut as percentage of the total corneal thickness in the center and periphery was 70.4% +/- 4.5% and 55.6% +/- 5.9%. Scanning electron microscopy images of the stromal bed showed a relatively smooth surface. CONCLUSION: The femtosecond laser is effective to prepare a deep horizontal lamellar cut in a standardized method. The stromal bed is smooth and without extensive adjacent tissue damage. The is thinner in the center and thicker at the edges, which may produce a mild hyperopic shift after femtosecond laser-assisted Descemet's stripping endothelial keratoplasty.

Results of cataract surgery after implantation of an iris-fixated phakic intraocular lens.

PURPOSE: To report the results of cataract surgery after previous implantation of an Artisan iris-fixated phakic intraocular lens (pIOL) for the correction of myopia. SETTING: University center and private practice. METHODS: This study comprised eyes with previous implantation of an iris-fixated pIOL to correct myopia and subsequent pIOL explantation combined with cataract surgery and in-the-bag implantation of a posterior chamber IOL. Predictability of refractive results, changes in endothelial cell density (ECD), and postoperative best corrected visual acuity (BCVA) were analyzed. RESULTS: The mean follow-up after cataract surgery in the 36 eyes of 27 consecutive patients was 5.7 months +/- 7.5 (SD). The mean time between pIOL implantation and cataract surgery was 5.0 +/- 3.4 years. After explantation of the pIOL and subsequent cataract surgery, the mean spherical equivalent (SE) was -0.28 +/- 1.11 diopters (D); the SE was within +/-1.00 D of the intended correction in 72.2% of patients and within +/-2.00 D in 86.1% of patients. The mean endothelial cell loss after the combined procedure was 3.5% +/- 13.2% and the mean postoperative BCVA, 0.17 +/- 0.18 logMAR. CONCLUSIONS: In patients with a history of implantation of an iris-claw pIOL for the correction of myopia, cataract surgery combined with explantation of the pIOL yielded acceptable predictability of the postoperative SE and minimal loss of ECD, resulting in a gain in BCVA.

A systematic review on the effect of bevacizumab in exudative age-related macular degeneration.

AIM: To provide evidence for the effect of bevacizumab on visual acuity (VA) and central retinal thickness (CRT) in exudative age-related macular degeneration METHODS: A systematic review of all articles of bevacizumab for exudative AMD was conducted. Articles published up to March 2008 were identified in Medline, Embase, the Cochrane Controlled Trials Register and references from included articles. Search terms were "Bevacizumab or Avastin" and "Macula* or ARMD or AMD or intra(-)vitreal or intra(-)vitreous". Three observers participated in the data retrieval and assignment of the quality scores. RESULTS: A total of 561 articles were retrieved. Three randomised controlled trials (RCT) and 23 before-and-after studies of patients (n = 1,435) who had received bevacizumab were published. Inclusion criteria varied. Lack of masking was the main methodological shortcoming. These RCTs showed that bevacizumab is more effective than PDT. Bevacizumab was given intravenously or as intravitreal injection. The latter was given once, or repeatedly every 4 weeks, and with or without additional injection when a recurrence occurred, mostly based on visual acuity and/or findings from optical coherence tomography. After intravenous administration, the weighted mean change in VA was +12.8 ETDRS letters (range +11 to +14) and the weighted mean change for CRT was -129 microm (range -100 to -202). For the 23 studies with intravitreal injections, the change in VA was +8.6 letters (range +2 to +26) and the change in CRT was -90 microm (range -46 to -190). The incidence of adverse events was low. The change in VA was 2.7 letters higher for studies with a higher quality vs lower quality. CONCLUSION: Visual acuity improves and central retinal thickness decreases in patients with exudative AMD after bevacizumab. There is no reasonable doubt that this is caused by bevacizumab. It is likely that a randomised controlled trial will show that bevacizumab is equivalent in effect to ranibizumab, which showed a change in ETDRS of +5.9 letters for occult or minimally classic CNV and +9.8 letters for classic CNV after three monthly injections in two large RCTs.

Influence of anterior chamber morphometrics on endothelial cell changes after phakic intraocular lens implantation.

PURPOSE: To analyze the position of iris-fixated phakic intraocular lenses (pIOLs) using anterior segment optical coherence tomography (AS-OCT) and evaluate the effect of anterior chamber morphometrics on endothelial cell changes. SETTING: Department of Ophthalmology, Academic Hospital Maastricht, The Netherlands. METHODS: In this cross-sectional study, AS-OCT was used to measure the distances from the center and the edges of the pIOL to the corneal endothelium in 242 eyes with various models of myopic pIOLs. Endothelial cell measurements were performed preoperatively and at each follow-up examination. RESULTS: The mean follow-up was 34.1 months+/-24.7 (SD) (range 3 months to 7 years). The mean distance between the edge of the pIOL and the endothelium was 1.37+/-0.22 mm. Although this distance was smaller than the safety value of 1.50 mm in 68.6% of the eyes, no eye developed corneal decompensation. There was a significant endothelial cell density (ECD) loss of 1.28%+/-8.46%, 3.25%+/-8.24%, and 5.02%+/-10.40% at 2 years, 5 years, and 7 years, respectively. Linear mixed-model analysis predicted a yearly ECD loss of 0.98% for a mean edge distance of 1.37 mm, 0.15% for an edge distance of 1.59 mm (mean plus 1 SD), and 1.80% for an edge distance of 1.15 mm (mean minus 1 SD). CONCLUSIONS: A shorter distance between the edge of the pIOL and the endothelium was significantly associated with higher ECD loss. For safety reasons, the postoperative examination should include long-term evaluation of the anterior chamber morphometrics in addition to ECD counts.