Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.

The effect of phacoemulsification and combined phaco/glaucoma procedures on the intraocular pressure in open-angle glaucoma. A review of the literature.

PURPOSE: This review article addresses the different aspects that influence the choice and sequence of surgical treatment in patients with coexisting open-angle glaucoma and cataract. The effect of phacoemulsification on the intraocular pressure (lOP) and on a preexisting bleb is discussed and phacotrabeculectomy and trabeculectomy are compared. Moreover, the most recent surgical pressure lowering techniques in combination with phacoemulsification are reviewed: iStent, Trabectome, Hydrus, Cypass and Canaloplasty. METHODS: Medline database was used to search for relevant, recent articles. CONCLUSION: A sustained IOP decrease of 1.5 mmHg can be expected after a phacoemulsification in patients with open-angle glaucoma. The higher the preoperative pressure, the greater the IOP lowering will be. A phacoemulsification on a trabeculectomized eye will often lead to reduced bleb function and an IOP rise of on average 2 mmHg after 12 months. Compared to a trabeculectomy, phaco-trabeculectomy will have a less IOP lowering effect and a higher complication rate. iStent and Trabectome combined with phacoemulsification can decrease the IOP with 3 to 5mmHg, with a low complication rate. The combination of Cypass and Hydrus with phaco-surgery may have a more significant IOP lowering effect but long term results are not yet published. Combining Canaloplasty with phacoemulsification is a more challenging surgery but if a tension suture can be placed, an IOP decrease around 10 mmHg might be expected.

Anterior segment ischemia with rubeosis iridis after a circular buckling operation treated successfully with an intravitreal bevacizumab injection: a case report and review of the literature.

PURPOSE: To report a case of anterior segment ischemia (ASI) with rubeosis iridis after circular buckling surgery in a highly-myopic patient which was successfully treated with a second intravitreal bevacizumab injection. METHODS: Case report and review of the literature. DISCUSSION: ASI is a rare but potentially serious complication of posterior segment surgery. Finally it leads to neovascular glaucoma as a result of rubeosis iridis. An encircling band can compromise anterior segment circulation in different ways: by manipulation or disinsertion of the recti muscles, by occlusion of the vortex veins through compression or by changes in the blood supply of iris and ciliary body. This patient developed rubeosis iridis secondary to ASI. There was a remarkable regression of rubeosis iridis one month after a second intravitreal bevacizumab injection. Other case reports of bevacizumab use in neovascular glaucoma have shown clinical improvements of these patients, with intraocular pressure control and reduction of the neovascularization process. CONCLUSION: We describe a highly-myopic patient who developed ASI with rubeosis iridis after a circular buckling operation. Slit-lamp examination and gonioscopy can show very little rubeosis iridis and can be misleading. Iris fluorescein angiography is the most sensitive technique for evaluation of iris vessel abnormalities and is of considerable value in the early detection of rubeosis iridis. This report demonstrates the rapid resolution of rubeosis iridis on iris fluorescein angiography after a second intravitreal injection of bevacizumab. How long this regression will persist is unknown and repeated injections of bevacizumab may be necessary if rubeosis reappears.

The challenges of monitoring glaucoma progression.

Diagnosing glaucoma progression is complex: it requires the precise assessment of functional loss and structural change compared with baseline measurements. Establishing reliable baseline data is essential in this process. Determining a functional baseline requires repeated visual field testing, while documentation of the optic disc appearance is needed for the acquisition of a structural baseline. The latter can be achieved using both clinical and imaging methods, which are complementary. Although imaging-based modalities to assess absolute and rate of progression are likely to prove more important in the future, more guidance is currently required for their use in clinical practice. Because the rate of progression provides important information about the risk of vision loss, guidelines recommend determining the rate of progression for each individual patient when planning management. Adherence issues must be addressed before changing the treatment strategy, since poor compliance can play a considerable role in many patients' disease progression. In conclusion, we must strive to improve the management of glaucoma to limit the impact disease progression has on the patient's quality of life.

Appraisal of optic disc stereo photos pre- and post-training session.

PURPOSE: To determine whether the diagnostic accuracy of judging serial optic disc color stereo photographs for glaucomatous change by non-expert ophthalmologists changed after a training session. METHODS: 24 ophthalmologists in training at the University Hospitals Leuven classified 50 eyes with varying severity of glaucoma as stable or progressing based on the appraisal of serial optic disc stereo photographs. A comparison between the diagnostic accuracy of residents (n=18) and trainees (n=6) was made before and after a training session. RESULTS: The mean agreement (kappa) with the reference standard before training was lower for the trainees than for the residents. The mean kappa before training was 0.37 for the residents and 0.29 for the trainees (p = 0.18). The mean agreement with the reference standard improved significantly after a training (from 0.29 to 0.56 [p = 0.031 for the trainees, and from 0.37 to 0.48 for the residents [p = 0.005]). The overall mean kappa was 0.35 pre-training and 0.50 post-training (p < 0.001). CONCLUSIONS: The agreement and diagnostic accuracy of residents in training in appraising serial optic disc photos improved significantly after a training session.

Reversal of optic disc cupping with improvement of visual field and stereometric parameters after trabeculectomy in young adult patients (two case reports).

The authors report two cases of mid- to long-term reversal of optic disc cupping after trabeculectomy with mitomycine-C in young adult patients suffering from secondary glaucoma. The cup to disc ratio reversed from 0.80 and 0.60 to 0.65 and 0.40 respectively and remained unchanged until the last follow-up visit at 6 and 36 months respectively. Concomitantly, there was an improvement of the visual field and of the optic disc stereometric parameters on the Heidelberg Retina Tomograph.

Glaucoma medication during pregnancy and nursing.

Risks that glaucoma medications pose to the fetus and neonate must be balanced against the risk of vision loss in the mother. There is no high level evidence for harmful effects on the fetus and neonate of medications used to treat glaucoma. All topical and systemic glaucoma medication should be avoided during the first trimester of pregnancy. Systemic carbonic anhydrase inhibitors, topical prostaglandin analogues and antimetabolites during surgery should be avoided absolutely. Some topical medications are deemed compatible with lactation by the American Academy of Pediatrics, however, caution should still be practiced.

Ahmed and Baerveldt glaucoma drainage implants: long-term results and factors influencing outcome.

PURPOSE: To evaluate the clinical outcome of patients who received an Ahmed or Baerveldt implant for refractory glaucoma at the University Hospitals Leuven and to identify the factors which may influence the outcome. METHODS: Retrospective study including 62 eyes with uncontrolled glaucoma, who underwent the implantation of a drainage device between January 2002 and December 2008. Criteria for complete success were an intraocular pressure (IOP) < or = 21 mmHg and > 5 mmHg, and a minimum 20% decrease in IOP compared to baseline, without additional medications at 2 consecutive visits after 3 months. Qualified success was defined as the same criteria with additional medications. If these criteria were not met, if additional glaucoma surgery was needed, or if the eye became phtitic, the case was classified as failure. Other outcome measurements were IOP reduction, additional glaucoma medications at the last follow-up, visual acuity, visual field, and complications. RESULTS: Over a mean follow-up period of 25 +/- 21,91 months, the mean intraocular pressure decreased from 27,98 +/- 6,5 mmHg to 15,2 +/- 5,87 mmHg (mean drop of 45%) at the last visit. Overall success (i.e. with or without medication) was 67.3%. Visual acuity improved or remained unchanged in 52/62 (83,9%) of patients. Eight patients (12,9%) had complications with significant visual loss (at least two Snellen lines worse) and five patients (8,1%) needed further surgery due to complications. No significant outcome predictors could be established. CONCLUSION: Ahmed and Baerveldt implants are a safe and effective procedure for lowering the IOP in the management of refractory glaucoma.

The iStent trabecular micro-bypass stent: a case series.

PURPOSE: To evaluate the safety and effectiveness of a trabecular micro-bypass stent, the iStent (Glaukos, USA), for reduction of intraocular pressure in patients with open angle glaucoma. METHODS: In this prospective case series, ten eyes of eight patients underwent a gonioscopically-guided implantation of an iStent. Six eyes underwent combined surgery: cataract surgery followed by iStent implantation, and the remaining four eyes underwent iStent implantation only. The primary outcome measure was intraocular pressure and the secondary outcome measures were the reduction in number of glaucoma medications, and the number of complications. RESULTS: Mean intraocular pressure dropped from 19.6 mmHg preoperatively to 16.3 mmHg (range 12-27) after one month (p = 0.04), to 15.4 mmHg (range 8-23) after six months (p = 0.03) and 15.8 mmHg (range 9-25 mmHg) after one year (p = 0.03). There was a significant reduction in number of hypotensive medications between baseline and 12 months postoperatively from 2.7 to 1.7 medications. No vision-threatening complications were observed. CONCLUSIONS: The Glaukos iStent trabecular micro-bypass implantation is a safe procedure that is not associated with complications traditionally associated with filtering surgery. This trabecular bypass results in significant mid-term reduction of intraocular pressure as well as the number of medications.

Allergic reaction to hyaluronidase after retrobulbar anaesthesia: a case series and review.

BACKGROUND: The enzyme hyaluronidase (HA) is an adjunctive in retrobulbar anaesthesia (RA) that is used during ophthalmic surgery to improve the efficacy and speed of nerve blocks. Although uncommon, HA has been shown to be a potential cause of allergic responses. CASE REPORTS: We describe three patients who experienced an allergic reaction to HA following ocular surgery in our department and provide an extensive overview of the literature on HA in RA. CONCLUSIONS: Although rare and mostly benign, allergy to HA should be included in the differential diagnosis when chemosis, proptosis and restriction of eye movements occur after parabulbar or retrobulbar anaesthesia. The authors feel that the beneficial effect of HA in small volumes of RA warrants its use despite this potential complication.

Is pulse synchronized pneumotonometry more reproducible than routine pneumotonometry and more in agreement with Goldmann applanation tonometry?

PURPOSE: This study compared the variability of intraocular pressure (IOP) measurements taken with pulse synchronized pneumotonometry (PNT) and with routine PNT (without pulse synchronization) and evaluated the agreement between PNT and Goldmann applanation tonometry (GAT). METHODS: In this prospective study, 148 eyes from 78 patients were enrolled. Patients were randomized into two groups. In the first group (A), the sequence of measurements was pulse synchronized PNT, routine PNT, and GAT. In the second group (B), the sequence of measurements was routine PNT, pulse synchronized PNT, and GAT. The mean of three measurements was averaged for PNT and GAT. All the measurements were performed by the same investigator, who was masked to GAT measurements. The mean IOP measurements and intrapatient standard deviations among the three tonometers were compared using analysis of variance measurement. Bland & Altman plots were used to assess the agreement between PNT and GAT. RESULTS: The variability of IOP measurements taken with pulse synchronized PNT was significantly lower than with routine PNT in both groups (1.2+/-0.7 vs 1.3+/-0.7 mmHg in group A and 1.1+/-0.9 vs 1.3+/-1.0 mmHg in group B [p<0.001], respectively). PNT measurements with and without pulse synchronization were on average +/-2 mmHg higher than GAT measurements in both groups (p<0.001). The 95% limits of agreement between PNT and GAT varied between -3.8 and 8.5 mmHg. CONCLUSIONS: Pulse synchronized PNT gives more reproducible measurements than routine PNT. The agreement between PNT and GAT is poor.

Ocular symptoms and signs with preserved and preservative-free glaucoma medications.

PURPOSE: To compare the prevalence of side effects between eyedrops with or without preservatives, in terms of subjective symptoms and objective signs in patients with open-angle glaucoma. METHODS: In a multicenter cross-sectional epidemiologic survey in four European countries, ophthalmologists in private practice enrolled 9658 nonconsecutive patients using preservative (P) or preservative-free (PF) beta-blocking eyedrops between June 1997 and December 2003. Subjective symptoms, conjunctival and palpebral signs, and superficial punctate keratitis were explored before and after a change in therapy. For statistical analysis, a Chi-square test was used to calculate the differences in the prevalence of symptoms and signs with or without preservatives. RESULTS: A total of 74% of the patients used P, 12% PF, 10% a P-PF combination, and in 4% the type of medication was unknown. Each recorded symptom and all the palpebral, conjunctival, and corneal signs were significantly more frequent (p<0.0001) in the P-group than in the PF-group, such as pain or discomfort during instillation (48 vs 19%), foreign body sensation (42 vs 15%), stinging or burning (48 vs 20%), and dry eye sensation (35 vs 16%). A total of 68% of the patients had a sec-ond visit performed, of whom 63% (6083) had been evaluated on treatment difference. A significant decrease (p<0.0001) of all ocular symptoms and signs was observed in patients in whom the preserved eyedrops were diminished in number or altered into preservative free drops. CONCLUSIONS: Compared to preserved eyedrops, preservative free eyedrops are significantly less associated with ocular symptoms and signs of irritation.

Acute visual field constriction in optic disc drusen: report of an unusual case.

We describe a case of an acute symptomatic and non-progressive visual field constriction in one eye of a 19-year-old female with optic disc drusen. The fellow eye showed slowly progressive visual field defects. A limited or retrolaminar infarction of the optic nerve head seems a plausible cause of the acute visual field loss. The slow progression in the fellow eye is most probably due to mechanical compression by the drusen. The case is documented with Humphrey perimetry during a follow-up of 11 years and with Color Doppler Imaging (CDI) of the optic nerve.

Safe trabeculectomy technique: long term outcome.

AIM: To assess the long term outcome of a new trabeculectomy technique. METHODS: Trabeculectomy was performed using a fornix based conjunctival flap, an anterior chamber maintainer, a standardised punch technique, and a combination of adjustable and releasable sutures in 56 eyes of 53 patients. The main outcome measures were the postoperative intraocular pressure (IOP) and the frequency of early postoperative complications. The mean follow up time was 15.7 (range 12-21) months. RESULTS: The mean preoperative and postoperative IOP at 12 months were 21.2 (SD 6) and 12.8 (3.0) mm Hg, respectively. All patients had an IOP of <21 mm Hg, 90.9% had an IOP <18 mm Hg, and 61.4% had an IOP <14 mm Hg. Postoperative complications were infrequent: flat anterior chamber (1.8%), bleb leakage (0%), or hypotony (1.5%) beyond 3 weeks, or choroidal detachment at any time point (8.9%). CONCLUSIONS: This novel trabeculectomy method offers the possibility to tailor the IOP postoperatively with a minimum of postoperative complications and excellent IOP control at the long term follow up.

Late-onset capsular bag distention syndrome after cataract surgery: 2 case-reports.

Late capsular bag distension syndrome occurs most of the time with the accumulation of opaque milky fluid behind the IOL, without refractive change, like in one of our cases. The other case that we will describe had an accumulation of a clear fluid behind the IOL with an induced hyperopia. To the best of our knowledge, this is the first published report of capsular bag distension syndrome with a shift towards hyperopia. In both case the visual acuity and the initial refraction was restored after Nd:YAG posterior capsulotomy.

Argon versus selective laser trabeculoplasty.

PURPOSE: To compare conventional argon laser trabeculoplasty (ALT) with selective laser trabeculoplasty (SLT) in terms of their efficiency in lowering the intra-ocular pressure. METHODS: In this retrospective study, 56 eyes from 44 patients with primary open angle glaucoma, ocular hypertension, pseudo-exfoliative (PXF) or pigment dispersion glaucoma (PDG) were included. Patients underwent either ALT (n=18) or SLT (n=38). The intraocular pressure (IOP) was measured immediately prior to and 3 to 5 weeks after the theraPY. RESULTS: At 3 to 5 weeks the lOP-reduction was 22.4% after ALT and 15.5% after SLT (p = 0.141). Of note, of the four patients with PDG 2 underwent ALT and 2 SLT. Remarkably, both patients who had had SLT showed a paradoxical rise in lOP after the procedure (+15.5%). When these patients were excluded from the analysis, a similar hypotensive efficacy was found between ALT (-19%) and SLT (-17.9%) (p = 0.836). A small additional study with lower energy levels (< 0.9 mJ) confirmed the paradoxical IOP rise in 6 patients with heavily pigmented angles (2 with PDG and 2 with PXF) (+19.2%). It occurred in the absence of steroid treatment and persisted until 12 weeks after treatment. CONCLUSIONS: The short term efficacy of ALT and SLT was similar. In this study, the patients with PDG who underwent SLT showed a paradoxical rise in IOR This finding may indicate that even lower energies (0.4 to 0.6 mJ) are required when performing SLT in patients with heavily pigmented trabeculae.

Screening for vascular risk factors in glaucoma: the GVRF study.

PURPOSE: To determine the prevalence of vascular risk factors (VRF) in patients with primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and ocular hypertension (OH), and to evaluate their influence in the progression of the disease. METHODS: 269 Belgian ophthalmologists were invited to participate in this cross-sectional prevalence study. Using a questionnaire the following parameters were analyzed in patients with POAG, NTG, and OH: age, intraocular pressure, refraction, visual field defect, vertical cup/disc ratio, medical therapy, and vascular risk factors. Progression of visual field was based on subjective analysis of minimum three reliable automated perimetries over a period of minimum three years. RESULTS: 4920 patients were enrolled in the study. 75% had POAG, 8% had NTG, and 17% had OH. The mean age was 67 years (40-99 y.). Fifty-three percent were female. There was a significant difference in the prevalence of no VRF vs. >1 VRF between the patients with OH and the patients with POAG/NTG (p < 0.01). Visual field progression was found in 34% of the patients with POAG and 46% of the patients with NTG. In the group with POAG the presence of at least 2 and at least 3 VRF increased the risk for visual field progression with respectively 16% and 42% compared to patients without VRF (p = respectively 0.03 and 0.002). CONCLUSIONS: The prevalence of VRF is significantly higher in patients with POAG/NTG compared to patients with OH. The presence of VRF might increase the risk for progression of glaucomatous visual field defects.

Needling-revision of failed filtering blebs.

PURPOSE: To investigate the efficacy and safety of needling-revision of failed blebs after trabeculectomy. METHODS: A retrospective chart review of 28 eyes of 28 patients who underwent a trabeculectomy with subsequent needling-revision between January 2002 and December 2003. The mean follow-up was 15 months after the first needling-revision. All interventions were conducted by the same surgeon. Absolute success was defined as an IOP <18 mmHg without medication or as an IOP reduction > 20% without medication if the preoperative IOP was < or = 21 mmHg. Relative success was defined as meeting these criteria with or without medication. RESULTS: The mean interval between trabeculectomy and the first needling-revision was 5 months. Repeated needling-revision (up to 3 times) was performed as clinically necessary. In 90% of the needling-revisions 5-FU was used to prevent postoperative fibrosis. The mean +/- SD IOP before needling-revision and at the last follow-up was respectively 24.7 +/- 6 and 15.7 +/- 3 mmHg (p<0.001) Needling-revision was an absolute success in 39% (11/28) and a relative success in 68% (19/28). Minor complications attributed to needling-revision occurred in 32% including self reabsorbing subconjunctival bleeding (1), filamental (1) and punctate keratitis (1), transient choroidal effusion (3), wound leak (4) and hyphaema (2). Progression of cataract occurred in 1 patient. A serious complication occurred in 1 case (hypotony with persistent macular oedema). CONCLUSIONS: Bleb needling-revision can prevent more invasive intervention in a significant number of patients with failed trabeculectomy blebs. Complications are similar to those seen after trabeculectomy.