Dexamethasone implant for non-infectious uveitis: is it cost-effective?

BACKGROUND: Uveitis is inflammation inside the eye. The objective of this study is to assess the cost-effectiveness of a dexamethasone implant plus current practice (immunosuppressants and systemic corticosteroids) compared with current practice alone, in patients with non-infectious intermediate, posterior or pan-uveitis and to identify areas for future research. METHODS: A Markov model was built to estimate the costs and benefits of dexamethasone. Systematic reviews were performed to identify available relevant evidence. Quality of life data from the key randomised-controlled trial (HURON) was used to estimate the interventions' effectiveness compared with the trial's comparator arm (placebo plus limited current practice (LCP)). The analysis took a National Health Service and Personal Social Services perspective. Costs were calculated based on standard UK sources. RESULTS: The incremental cost-effectiveness ratio (ICER) of one dexamethasone implant compared with LCP is estimated as £19 509 per quality-adjusted life year (QALY) gained. The factors with the largest impact on the results were rate of blindness and relative proportion of blindness cases avoided by dexamethasone. Using plausible alternative assumptions, dexamethasone could be cost saving or it may be associated with an ICER of £56 329 per QALY gained compared with LCP. CONCLUSIONS: Dexamethasone is estimated to be cost-effective using generally accepted UK thresholds. However, there is substantial uncertainty around these results due to scarcity of evidence. Future research on the following would help provide more reliable estimates: effectiveness of dexamethasone versus current practice (instead of LCP), with subgroup analyses for unilateral and bilateral uveitis, incidence of long-term blindness and effectiveness of dexamethasone in avoiding blindness.

ASSESSMENT OF ANATOMICAL AND FUNCTIONAL OUTCOMES WITH OCRIPLASMIN TREATMENT IN PATIENTS WITH VITREOMACULAR TRACTION WITH OR WITHOUT MACULAR HOLES: Results of OVIID-1 Trial.

PURPOSE: To evaluate the anatomical and functional outcomes with ocriplasmin in patients with vitreomacular traction (VMT) with or without macular hole (MH). METHODS: In a Phase 4, multicenter, single-arm, open-label study, eligible patients (VMT with focal adhesion, without epiretinal membrane, and with MH ≤400 µm [if present]) received a single intravitreal injection of ocriplasmin. Nonsurgical resolution of VMT (Day 28 [primary endpoint]), best-corrected visual acuity, MH closure, vitrectomy rate, and safety were assessed through Day 180. RESULTS: Overall, 466 patients were included in the full analysis set, of whom 47.4% had VMT resolution by Day 28; resolution rates in patients with VMT without MH, VMT with MH ≤250 µm, and VMT with MH >250 to ≤400 µm were 43.4%, 68.6%, and 62.7%, respectively. Macular hole closure was higher in eyes with VMT and MH ≤250 µm (57.1%) than in eyes with VMT and MH >250 to ≤400 µm (27.5%) at Day 28. Overall, 30.8% of patients with VMT resolution gained ≥10 letters in best-corrected visual acuity at Day 180. Adverse events were consistent with the known safety profile of ocriplasmin. CONCLUSION: Ocriplasmin is effective for resolution of VMT without or with MH (≤400 µm); treatment outcomes can be optimized with patient selection.

Assessment of diagnostic and therapeutic vitrectomy for vitreous opacity associated with uveitis with various etiologies.

Vitreous opacity (VO) is a common feature of intermediate uveitis, posterior uveitis, and panuveitis. Fundus observation is critical for determining the etiology of uveitis, however, is often interfered with VO. In these clinical settings, vitrectomy contributes to a correct diagnosis and guides alternative management strategies. The purpose of this study was to evaluate the diagnostic yield and surgical outcome of vitrectomy in uveitic patients with VO and compare the visual outcome between infectious and noninfectious uveitis. Forty-five eyes with uveitis-associated VO underwent diagnostic and therapeutic vitrectomy, and etiological diagnosis of uveitis was confirmed in 34 of 45 eyes (75.6%). The diagnoses were infectious uveitis in 13 eyes (28.9%), noninfectious uveitis in 21 eyes (46.7%), and unidentified uveitis in 11 eyes (24.4%). Visual acuity (VA) improvement rates at 6 months after surgery were 69.2%, 76.2%, and 90.9% in the infectious, noninfectious, and unidentified uveitis groups, with no significant difference among 3 groups. Significant decrease in inflammation score after vitrectomy was observed only in the infectious uveitis group. This study demonstrated that diagnostic vitrectomy for inflammatory eyes with VO of unknown etiology was effective in infectious and noninfectious uveitis, and the therapeutic effect of VA improvement was observed in both types of uveitis.

Ultrasonographical assessment of implanted biodegradable device for long-term slow release of methotrexate into the vitreous.

Our group has developed a biodegradable drug delivery device (micro-implant) for long-term slow intraocular release of methotrexate (MTX) that can be implanted in the peripheral vitreous. The purpose of this study was to assess the position of the implanted devices and the status of the adjacent vitreous and peripheral retina over time using B-scan ocular ultrasonography (US). In each of the eight New Zealand rabbits used in this study, a chitosan (CS) and poly-lactic acid (PLA)-based micro-implant containing approximately 400 µg of MTX and a placebo micro-implant without MTX were inserted into the peripheral vitreous of the right and left eyes, respective, employing minimally invasive surgery. B-scan US imaging was performed on all of the rabbits immediately after implant insertion and on two rabbits at each of several pre-determined time points post-insertion (post-insertion days 5, 12, 19, and 33) to evaluate the position of the micro-implants and identify any evident morphological changes in the micro-implants and in the peripheral retina and vitreous during treatment. US imaging revealed stable positioning of the PLA-coated CS-based MTX micro-implant and the placebo micro-implant in the respective eyes throughout the study and lack of any changes in size, shape or sonoreflectivity of the micro-implants or abnormalities of the peripheral vitreous or retina in any of the study eyes. In summary, US did not show any evident morphological changes in the micro-implants, shifts in post-insertion position of the micro-implants, or identifiable changes in the micro-implants or peripheral vitreous and retina of the study eyes.

In Vivo Assessment of Pharmacologic Vitreolysis in Rabbits With the Digital Fluoroscopy System.

PURPOSE: The purpose of this study was to demonstrate the efficacy of the digital fluoroscopy system (DFS) for the in vivo assessment of pharmacologically induced posterior vitreous detachment (PVD) and vitreous liquefaction in a rabbit model. METHODS: Twenty eyes from 10 New Zealand white rabbits were divided into 5 groups. In each group, one rabbit received an intravitreal injection of 2.0 U plasmin in the right eye and 0.5 U plasmin in the left eye. Intravitreal injection of 0.1 mL balanced salt solution (BSS) was given in the right eye, and no injection was given in the left eye of another rabbit used as a control. Intraocular fluid dynamics were assessed by the DFS, using a contrast agent in each group at different time intervals (6 hours, 12 hours, 1 day, 3 days, and 7 days). After rabbits were killed, both eyes were enucleated. Scanning electron microscopy was used to confirm the morphological alterations of the vitreoretinal interface as observed in the DFS. RESULTS: Complete PVD was observed after 12 hours with 2.0 U plasmin injection, whereas complete PVD was observed only after 3 days in eyes injected with 0.5 U plasmin. Eyes that received BSS injection or did not receive an injection failed to show complete PVD even after 7 days. Complete vitreous liquefaction was observed after 7 days with 2.0 U plasmin injection, but no eyes with 0.5 U plasmin or BSS injection showed complete liquefaction. We could clearly confirm the presence of PVD and the degree of vitreous liquefaction by using DFS. CONCLUSIONS: Digital fluoroscopy system appears to be a useful tool for the evaluation of pharmacological vitreolysis in rabbits with clear in vivo visualization of PVD and vitreous liquefaction.

Intravitreal docosahexaenoic acid in a rabbit model: preclinical safety assessment.

PURPOSE: The purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA) in rabbit eyes over a short-term period. METHODS: Sixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain) were prepared: 10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intravitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histological examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis was performed by SPSS 21.0. RESULTS: Slit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µ) Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected groups except for the group injected with 50 µg/50 µl. CONCLUSIONS: Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 µg/50 µl. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination, of different retinal diseases.

[Early treatment of exudative age-related macular degeneration with ranibizumab (Lucentis®): the key to success]. / Frühzeitige Behandlung mit Ranibizumab (Lucentis®) bei exsudativer AMD: Voraussetzung für einen Erfolg.

BACKGROUND: Intravitreal ranibizumab (Lucentis®) is an effective treatment for exudative age-related macular degeneration (AMD). Up to now, settlement for this therapy remains quite complex and is handled differently by insurance companies as well as in the different German states. Often applications must be submitted and approved before an injection can be made. This procedure is time consuming and a delay in starting treatment might result. The aim of this study was to determine the effect of late-onset injection on visual acuity before and during the upload procedure. METHODS: All patients treated with ranibizumab intravitreally between February 2007 and May 2010 were retrospectively evaluated for their best-corrected visual acuity at the day of diagnosis, injections during the upload phase and first follow-up visit after upload. RESULTS: A total of 1,149 eyes were evaluated and divided into 2 groups according to time between diagnosis and first injection (group 1: ≤10 days, group 2: >10 days). There was no statistically significant difference between the groups for average age, gender, visual acuity at day of diagnosis and type of choroidal neovascularisation. However, both groups differed in the loss of visual acuity before the first injection and the possible increase in visual acuity. Group 1 waiting ≤10 days showed - in contrast to group 2 waiting >10 days--a smaller loss of visual acuity before upload and greater gain of visual acuity during upload. Those differences were statistically significant. CONCLUSION: Successful treatment of exudative AMD requires small intervals between diagnosis and first ranibizumab injection. After diagnosis, the first injection with ranibizumab should be given as early as possible.

[Visual self-assessment with the ACTO test during follow-up of AMD patients after intravitreal injections]. / Eigenerhebung der Leseleistung mit dem ACTO-Selbsttest bei AMD-Patienten nach intravitrealen Injektionen.

INTRODUCTION: Monthly controls are necessary after injections of vascular endothelial growth factor (VEGF) to enable timely recognition of a renewed decrease in vision. However, these monthly control intervals are not realistic for many older patients with age-related macular degeneration (AMD), and outpatient clinics often reach their logistical limits because of inadequate funding for the additional medical work. Against this background, we conceived the ACTO self-test as a novel screening method for patients to discover unnoticed visual changes outside the routinely scheduled ophthalmic examination. MATERIAL AND METHODS: The paper version of the ACTO self-test consists of a reading chart gradated in decimal steps as well as six questions regarding the quality of the Amsler grid. The patient uses a self-screening test to examine each eye separately and then transfers the results to a table. Along with the self-examination, the Action Eyesight Service Center is available to the patient by phone to motivate the patient and schedule a new appointment if improved test results occur. If decreased values or suspected decreased visual function occur, these are verified immediately by the referring physician. RESULTS: There is a good correlation between the steps of the ACTO self-test and standard visual acuity at 4 m (r(2)=0.9). Altogether, 1,444 patients were followed by phone and 745 participated in repeated regular audits, for a total of 3,003 phone contacts. The treating physician was informed about decreased visual acuity or increased Amsler distortion in the ACTO test in 137 cases, and immediate verification was done. We had 699 dropouts; the reasons were decreased visual acuity below the limits of the ACTO test in 39%, additional monthly examinations by the local ophthalmologist in 29%, and a desire for no more telephone follow-up (despite initial written consent) in 32%. Decreased vision when reading or an increased score on the Amsler test within the ACTO screening test was observed in 18% of AMD patients during the maintenance phase. CONCLUSION: Monthly screening by the ACTO screening test in combination with phone audits offers a new way to test visual acuity, with the Amsler score helping to detect changes in visual function. For patients with visual changes, confirmation by the ophthalmic physician can be achieved in time. Self-assessment cannot replace qualified ophthalmologic examination, but monthly self-controls enhance safety, reduce the number of physician contacts, and improve the detection of visual changes, with the option of immediate ophthalmic retreatment.