Standardized care by redesign of an intravitreal injection pathway.

PURPOSE:: Intravitreal injection of medication is a rapid rising surgical intervention in modern ophthalmological care. With increasing numbers, the caseload of complications follows and the burden on daily clinical organization increases. This study focuses on developing a standardized treatment protocol to improve care and reduce hazard. METHODS:: A standardized treatment protocol was designed and educated to the involved medical doctor and registered nurse. An independent observer used this protocol to evaluate the actions performed during the intravitreal injection. Data on the included patients and products injected were collected. RESULTS:: In total, 180 injections of 134 patients were observed between 1 December 2011 and 18 October 2012, divided over 16 measurements. From the fifth measurement on, a 100% protocol adherence for the time out procedure was achieved and maintained over time, with a transient insignificant decrease. The performance of actions of the medical doctor and assisting registered nurse followed the same trend with a rapid increase and 100% protocol adherence. No microorganism caused development of endophthalmitis was recorded. CONCLUSION:: The optimization of an intravitreal injection care pathway leads to a more standardized intervention process with no apparent reduction in clinical efficiency and safety.

Non-organic visual loss in children: prospective and retrospective analysis of associated psychosocial problems and stress factors.

PURPOSE: To report on the prevalence of non-organic visual loss (NOVL) and its associated psychopathology and psychosocial stress factors on children presenting with visual problems without an obvious cause at a routine ophthalmological examination. METHODS: One hundred and seventy children presented at our paediatric ophthalmology department between 2007 and 2014 with visual loss. Routine examination showed no obvious underlying cause. Pattern-onset visual-evoked potentials (pVEPs) were performed to obtain an objective visual assessment. Selected patients underwent more investigations, and follow-up was organized in every child to differentiate organic visual loss (OVL) from NOVL. In the NOVL group, we retrospectively analysed the medical file data and prospectively the questionnaires completed by patients and their parents. RESULTS: Eighty-five children (50%) were diagnosed with OVL, the other 50% of children were diagnosed with NOVL. In the latter, girls predominated and the mean age was 11.0 years. The most common presenting symptom was binocular reduced visual acuity. pVEPs were normal in all patients. We categorized associated comorbidity in the NOVL group in three subgroups: malingering, psychosocial stressors and child psychiatric disorders. CONCLUSION: Non-organic visual loss in children is a common diagnosis in clinical practice. The diagnosis is made by recognition of characteristic features and by exclusion of organic disease. pVEP is a useful tool to obtain an objective visual acuity and to differentiate functional from organic vision loss. The prognosis in NOVL is good with a spontaneous recovery in the majority of patients. Ophthalmologists should be aware of possible underlying psychosocial and psychiatric disorders; referral can be necessary.

Clinical presentation, pathological features and natural course of metastatic uveal melanoma, an orphan and commonly fatal disease.

BACKGROUND: Uveal melanoma (UM) is a rare disease characterized by an unpredictable course and a variable outcome. We assessed the natural course of patients with metastatic uveal melanoma (MUM). METHODS: Data from 76 patients with MUM who were treated in Leuven between 1957 and 2008 were examined retrospectively. Statistical analysis involved the nonparametric, Kaplan-Meier and log rank tests. RESULTS: The median age at diagnosis of UM was 58 years (range 30-94). Synchronous metastases were found in 9% of the cases; all other patients had metachronous disease after a median interval of 40 months (range 7-420). Statistical analysis failed to identify factors related to the time until metastatic spread with the exception of a significant negative correlation with age at UM diagnosis (Spearman: ρ = -0.4, p < 0.001). The most frequent metastatic site was the liver (in 96% of the patients). The median time from diagnosis of UM until death was 47 months (range 2-236) and only 5 months in patients with metastatic disease (range 1-128). CONCLUSIONS: MUM is an orphan disease. Advances in MUM can only be achieved by the networking of sites interested in this rare tumor type, with systematic collection of data and tumor tissue for improving our understanding of the molecular biology of this disease.

Visual space and object space in the cerebral cortex of retinal disease patients.

The lower areas of the hierarchically organized visual cortex are strongly retinotopically organized, with strong responses to specific retinotopic stimuli, and no response to other stimuli outside these preferred regions. Higher areas in the ventral occipitotemporal cortex show a weak eccentricity bias, and are mainly sensitive for object category (e.g., faces versus buildings). This study investigated how the mapping of eccentricity and category sensitivity using functional magnetic resonance imaging is affected by a retinal lesion in two very different low vision patients: a patient with a large central scotoma, affecting central input to the retina (juvenile macular degeneration), and a patient where input to the peripheral retina is lost (retinitis pigmentosa). From the retinal degeneration, we can predict specific losses of retinotopic activation. These predictions were confirmed when comparing stimulus activations with a no-stimulus fixation baseline. At the same time, however, seemingly contradictory patterns of activation, unexpected given the retinal degeneration, were observed when different stimulus conditions were directly compared. These unexpected activations were due to position-specific deactivations, indicating the importance of investigating absolute activation (relative to a no-stimulus baseline) rather than relative activation (comparing different stimulus conditions). Data from two controls, with simulated scotomas that matched the lesions in the two patients also showed that retinotopic mapping results could be explained by a combination of activations at the stimulated locations and deactivations at unstimulated locations. Category sensitivity was preserved in the two patients. In sum, when we take into account the full pattern of activations and deactivations elicited in retinotopic cortex and throughout the ventral object vision pathway in low vision patients, the pattern of (de)activation is consistent with the retinal loss.

Physiological constraints for an intraocular inductive distance sensor.

In this paper the design restrictions of an inductive sensor for an intraocular lens with focus control on the basis of a marker implanted in the ciliary muscle of the eye are discussed in the framework of anatomical and physiological influences and constraints: limitations on the marker size, influences of tissue conduction and effects of off-axis implantation of the marker with respect to the coil.

Intracameral bevacizumab as an adjunct to trabeculectomy: a 1-year prospective, randomised study.

AIMS: To investigate the efficacy and safety of a single intracameral bevacizumab injection to improve the outcome of trabeculectomy. METHODS: A 12-month, prospective, randomised, double-masked, placebo-controlled trial. Patients with medically uncontrolled open-angle glaucoma scheduled for a primary trabeculectomy were recruited and randomised to receive 50 µL of either bevacizumab (1.25 mg) or placebo (balanced salt solution) peroperatively. Absolute success was defined as intraocular pressure (IOP) ≤18 mm Hg and >5 mm Hg with at least 30% reduction from baseline and no loss of light perception. Success through the use of additional medical and/or surgical IOP-lowering treatments was defined as qualified success. RESULTS: 138 patients completed a 12-month follow-up, 69 of whom were in the bevacizumab treated group. IOP at 1 year postoperatively was significantly lower than baseline (placebo: 25.6±9.9 mm Hg vs 11.5±3.9 mm Hg, p<0.01; bevacizumab: 24.8±8.1 mm Hg vs 11.9±3.8 mm Hg, p<0.01), with no difference between treatment groups (p=0.69). However, absolute success was higher in the bevacizumab group (71% vs 51%, p=0.02), with the need for IOP-lowering interventions (needlings) being lower in this group (12% vs 33%, p=0.003). Complication rates were low and comparable between groups. CONCLUSIONS: Peroperative administration of intracameral bevacizumab significantly reduces the need for additional interventions during the follow-up of patients undergoing trabeculectomy.

Intraocular electro-optic lens with ciliary muscle controlled accommodation.

In this paper a concept is proposed of an intraocular lens implant with electro-optic accommodation of a variable-focus hybrid liquid-crystal-based lens. The dioptric strength of the lens is electronically controlled by a signal that is derived from the change of inductance of a sensing coil due to a marker implanted in the nearby contracting or decontracting ciliary muscle. Analytical, numerical and experimental results are reported on the dependency of the frequency of a Colpitts oscillator circuit on the location of a nearby conductive marker. A concept is also reported on the use as an electro-optic lens of a device based on a liquid crystal in planar alignment, which is held between a flat and a curved window coated with optically transparent and electrically conductive layers.

Ophthalmological assessment of children with neurofibromatosis type 1.

UNLABELLED: Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder, caused by mutations in the NF1 gene, located on chromosome band 17q11.2. In 1988, the National Institutes of Health created specific criteria for the diagnosis of NF1. Four cardinal criteria are assessed through ophthalmological screening: Lisch nodules, optic pathway glioma, a distinctive osseous lesion (sphenoid dysplasia), and the (orbital) plexiform neurofibroma. NF1 patients are prone to the development of central and peripheral nervous system tumors. Especially young children are at risk for growing optic pathway gliomas that can threaten their sight. From an early age, children with NF1 undergo regular ophthalmological examinations. Little is known about the natural progress of these clinical features and the guidelines for screening and follow-up are controversial. Several questions remain unanswered. CONCLUSION: Most of these questions could be solved by better understanding of the natural history of optic pathway gliomas. There is a tendency towards using vision as a primary objective in clinical treatment trials; this way we can evaluate new treatment strategies and focus specifically on visual evolution so we will be able to select even more carefully which patient would benefit treatment. For future clinical trials, a standardized visual acuity assessment protocol is therefore mandatory.

Peculiar fundus abnormalities and pathognomonic electrophysiological findings in a 14-month-old boy with NR2E3 mutations.

Enhanced S-cone syndrome is a rare, slowly progressive autosomal recessively inherited retinal degeneration related to mutations in the NR2E3 gene. Patients often present with night blindness, visual loss and visual field abnormalities. Patients with enhanced S-cone syndrome exhibit a variable clinical phenotype associated with various degrees of pigmentary changes and foveal schisis. We report a 14-month-old boy with an unusual funduscopic appearance. The diagnosis of enhanced S-cone syndrome was suggested by the uniquely abnormal electroretinographic pattern and was confirmed by the finding of homozygous NR2E3 mutations.

Outcomes of different management options for malignant glaucoma: a retrospective study.

BACKGROUND: To assess the outcomes of the various medical and surgical treatment options for malignant glaucoma. METHODS: Design Retrospective, comparative case series. Participants Twenty-four eyes of 21 patients with malignant glaucoma. Intervention Nine eyes were treated medically. Twenty-one eyes underwent surgery, 15 of which had the full vitrectomy-(phaco)-iridectomy-zonulectomy procedure. Main outcome measures Intraocular pressure (IOP), best-corrected visual acuity (BCVA) and number of glaucoma medications were measured. RESULTS: The relapse rate was 100% after medical therapy, 75% after a Yag laser capsulotomy and a hyaloidotomy, 75% after a conventional vitrectomy and 66% after an anterior vitrectomy in combination with an iridectomy-zonulectomy. All patients who underwent a full vitrectomy combined with an iridectomy and a zonulectomy (and phacoemulsification if phakic) had postoperative relief of malignant glaucoma without relapse within the follow-up period. After this vitrectomy-tunnel technique, the IOP ranged from 10 to 22 mmHg (mean 16 mmHg) after a mean follow-up of 61 days. Mean BCVA improved by 5 Early Treatment Diabetic Retinopathy Study (ETDRS) lines, and mean number of glaucoma medications decreased from two to one. CONCLUSION: Complete vitrectomy combined with iridectomy and zonulectomy (and phacoemulsification, if applicable) most successfully managed aqueous misdirection syndrome in our retrospective case series.

The importance of keeping the chin up in graves orbitopathy.

A 42-year-old white woman suffering from mild euthyroid Graves orbitopathy for 6 years experienced recent-onset upper eyelid swelling, double vision, diminished vision, and reduced visual field of the right eye. Examination of the right eye showed decreased visual acuity, relative afferent pupillary defect, hypotropia with severely restricted elevation, upper visual field defect, impaired color contrast discrimination, and abnormal pattern visual evoked potential, but the Ishihara color plate reading and the optic disc appearance were normal. The left eye was normal, except for marked elevation restriction. On CT scan, the inferior rectus muscles were asymmetrically enlarged. These findings were suggestive of unilateral dysthyroid optic neuropathy, and a 2-week course of pulsed high-dose intravenous corticosteroids was subsequently administered. Since there was no improvement, the clinical examinations and tests were repeated, with the patient positioned in chin lift so that the right hypotropic eye was looking straight ahead. All tests normalized instantly and completely.

Evaluation of an international benchmarking initiative in nine eye hospitals.

BACKGROUND: Benchmarking has become very popular among managers to improve quality in the private and public sector, but little is known about its applicability in international hospital settings. PURPOSE: The purpose of this study was to evaluate the applicability of an international benchmarking initiative in eye hospitals. METHODOLOGY: To assess the applicability, an evaluation frame was constructed on the basis of a systematic literature review. The frame was applied longitudinally to a case study of nine eye hospitals that used a set of performance indicators for benchmarking. Document analysis, nine questionnaires, and 26 semistructured interviews with stakeholders in each hospital were used for qualitative analysis. FINDINGS: The evaluation frame consisted of four areas with key conditions for benchmarking: purposes of benchmarking, performance indicators, participating organizations, and performance management systems. This study showed that the international benchmarking between eye hospitals scarcely met these conditions. The used indicators were not incorporated in a performance management system in any of the hospitals. Despite the apparent homogeneity of the participants and the absence of competition, differences in ownership, governance structure, reimbursement, and market orientation made comparisons difficult. Benchmarking, however, stimulated learning and exchange of knowledge. It encouraged interaction and thereby learning on the tactical and operational levels, which is also an incentive to attract and motivate staff. PRACTICE IMPLICATIONS: Although international hospital benchmarking seems to be a rational process of sharing performance data, this case study showed that it is highly dependent on social processes and a learning environment. It can be useful for diagnostics, helping local hospitals to catalyze performance improvements.

Inhibition of vascular endothelial growth factor reduces scar formation after glaucoma filtration surgery.

PURPOSE: Filtration failure due to excessive postoperative scarring remains a major problem after glaucoma surgery. The authors have investigated whether glaucoma and filtration surgery are associated with increased levels of vascular endothelial growth factor (VEGF), and whether a humanized monoclonal antibody against VEGF, bevacizumab, can reduce postoperative scar formation and improve surgical outcome. METHODS: The levels of VEGF in samples of aqueous humor were measured by ELISA. The expression of the VEGF receptors Flt-1 and KDR was analyzed in cultured Tenon fibroblasts by real-time RT-PCR and Western blotting. The effect of VEGF and bevacizumab on Tenon fibroblasts in vitro was determined using a proliferation assay. The in vivo effect of the antibody was investigated in a rabbit model of trabeculectomy by measuring the intraocular pressure (IOP) and bleb area, and by immunohistological analysis of angiogenesis, inflammation, and fibrosis. RESULTS: VEGF levels were increased significantly in the aqueous humor of glaucoma patients and rabbits that had undergone surgery. Both VEGF receptors were expressed on Tenon fibroblasts. Fibroblast proliferation in vitro was stimulated by delivery of VEGF, and was inhibited by administration of bevacizumab. The antibody also reduced angiogenesis and collagen deposition significantly, and improved the outcome of glaucoma surgery in rabbits. CONCLUSIONS: VEGF was upregulated in the aqueous humor of glaucoma patients and in the rabbit model, and it stimulated fibroblast proliferation in vitro. This suggests that it is involved in the scarring process after filtration surgery. Bevacizumab reduced the proliferation of fibroblasts in vitro and improved surgical outcome.

Systemic absorption of 5-fluorouracil during vitrectomy.

PURPOSE: The aim of this study is to determine if systemic absorption is present after 5-fluorouracil (5FU) is used in the vitrectomy infusion. DESIGN: A two-case clinical study. METHODS: A catabolite of 5FU, alpha-fluoro-beta-alanine (FBAL), was measured in urine samples of two patients who underwent vitrectomy using 5FU in the infusion fluid. RESULTS: In both patients, FBAL was found in the urine samples collected up to 48 hours after the surgery, although in significantly different concentrations. CONCLUSIONS: The use of 5FU in the vitrectomy infusion fluid to prevent the formation of proliferative vitreoretinopathy may lead to significant general absorption and may be avoided in children and young adults.