Relationship between duration and extent of oedema and visual acuity outcome with ranibizumab in diabetic macular oedema: A post hoc analysis of Protocol I data

BACKGROUND/OBJECTIVES: This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO). SUBJECTS/METHODS: Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each study visit, averaged over the first 52 weeks). Associations between measures of residual oedema and best-corrected visual acuity (BCVA) were assessed in multiple regression analyses. RESULTS: Oedema duration and oedema extent during the first 52 weeks of ranibizumab treatment showed significant negative associations with BCVA improvement at weeks 52, 104 and 156. Eyes with the most persistent oedema gained (mean) 4.4 (95% CI 0.1─8.7) fewer Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 156 than eyes with the least persistent oedema (P = 0.044). Eyes with the greatest amount of oedema gained (mean) 9.3 (95% CI 4.0─14.5) fewer ETDRS letters at week 156 than eyes with the least amount of oedema (P \u3c 0.001). CONCLUSIONS: Macular oedema exposure over the first 52 weeks of ranibizumab treatment is a negative prognostic factor for long-term visual acuity improvement in centre-involved DMO

Pars plana vitrectomy in eyes containing a treated posterior uveal melanoma

To determine the safety of pars plana vitrectomy in eyes containing a treated posterior uveal melanoma. Interventional case series. Retrospective case series of patients with posterior uveal melanoma who underwent pars plana vitrectomy. Complications, vitreous cytology, local tumor control, and metastasis were assessed. Nine patients met study criteria. Tumors were treated with 125I plaque radiotherapy (seven patients) or transpupillary thermotherapy (two patients). Vitrectomy was performed for vitreous hemorrhage (five patients), macular pucker (two patients), macular hole (one patient), and rhegmatogenous retinal detachment (one patient). Vitrectomy was performed at a mean of 24.7 months (range, 7–47 months) after melanoma treatment. Dispersion of tumor cells at vitrectomy was not observed in any patients. Melanoma cells were detected in the vitreous aspirate in one of seven cases examined cytologically. This patient had intratumoral and vitreous hemorrhage before plaque radiotherapy, underwent combined vitrectomy/cataract extraction, and developed intraocular tumor dissemination 56 months after vitrectomy. No other patients developed intraocular tumor dissemination. At mean follow-up of 24 months (range, 3–63 months) after vitrectomy, none of the nine patients developed systemic metastasis. Pars plana vitrectomy rarely may lead to intraocular tumor dissemination, although the risk of this complication is probably low if the tumor has been treated and has responded to therapy before vitrectomy. Vitrectomy should be approached with caution if a vitreous hemorrhage is present, especially if the hemorrhage occurred before tumor treatment, as this may seed tumor cells into the vitreous cavity

Oxygen Distribution in the Human Eye: Relevance to the Etiology of Open-Angle Glaucoma after Vitrectomy

Oxidative damage is implicated in glaucoma. Vitrectomy, when followed by cataract surgery, causes glaucoma. Vitrectomy and cataract surgery increase oxygen in the anterior chamber angle, most likely by increasing oxygen diffusion from the ciliary body stroma

Two-year interim safety results of the 0.2 μg/day fluocinolone acetonide intravitreal implant for the treatment of diabetic macular oedema: The observational PALADIN study

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Background: The 0.2 μg/day fluocinolone acetonide (FAc) implant delivers continuous, low-dose, intravitreal corticosteroid for the treatment of diabetic macular oedema (DMO). This ongoing, 3-year, observational clinical trial provides long-term, real-world\u27safety results for the FAc implant in DMO. Methods: This 24-month interim analysis of a prospective, observational study investigated patients with DMO receiving the commercially available intravitreal 0.2 μg/day FAc implant. The primary outcome was incidence of intraocular pressure (IOP)-lowering procedures. Other IOP-related signals and their relationship to previous corticosteroid exposure, best-corrected visual acuity, central subfield thickness (CST), ocular adverse events and frequency of other treatments were also measured. Results: Data were collected from 95 previously steroid-challenged patients (115 study eyes) for up to 36 months pre-FAc and 24 months post-FAc implant. Mean IOP for the overall population remained stable post-FAc compared with pre-FAc implant. IOP-related procedures remained infrequent (two IOP-lowering surgeries pre-FAc; two trabeculoplasties and four IOP-lowering surgeries post-FAc). Mean visual acuity was stable post-FAc (mean improvement of 1-3 letters) and fewer DMO treatments were required per year following FAc implant. Mean CST was significantly reduced at 24 months post-FAc implant (p\u3c0.001) and the percentage of patients with CST ≤300 μm was significantly increased (p=0.041). Conclusion: Few IOP-related procedures were reported during the 24 months post-FAc implant. Positive efficacy outcomes were noted after treatment, with stabilisation of vision and reduction in inflammation, demonstrated by CST. The FAc implant has a favourable benefit-risk profile in the management of DMO, especially when administered after a prior steroid challenge. Trial registration number: NCT02424019

HUMAN INTRAOCULAR PENETRATION PHARMACOKINETICS OF MOXIFLOXACIN 0.5% VIA TOPICAL AND COLLAGEN SHIELD ROUTES OF ADMINISTRATION

PURPOSE: To determine penetration of moxifloxacin 0.5% into human aqueous and vitreous via topical and collagen shield routes of administration. METHODS: Moxifloxacin 0.5% was administered prior to vitrectomy surgery through one of three routes: topical drops every 2 hours for 3 days, versus topical drops every 6 hours for 3 days, versus delivery using a 24-hour dissolvable cross-linked corneal collagen shield. Aqueous and vitreous moxifloxacin concentrations were assayed using high-performance liquid chromatography RESULTS: Mean moxifloxacin concentrations in the every-2-hour group for aqueous (n = 9) and vitreous (n = 10) were 2.28 ± 1.23 μg/mL and 0.11 ± 0.05 μg/mL, respectively. Mean moxifloxacin concentrations in the every-6-hour group for aqueous (n = 10) and vitreous (n = 9) were 0.88 ± 0.88 μg/mL and 0.06 ± 0.06 μg/mL, respectively. Levels of minimum inhibitory concentration at which 90% of isolates are inhibited (MIC(90)) were far exceeded in the aqueous for a wide spectrum of pathogens that most commonly cause postoperative endophthalmitis. Moxifloxacin concentration in the vitreous did not exceed the MIC(90) for several key organisms. Delivery of moxifloxacin via a collagen shield revealed a mean aqueous concentration of 0.30 ± 0.17 μg/mL 4 hours after placement (n = 5). Vitreous levels at 4 hours, as well as aqueous and vitreous levels at 24 hours, were negligible using this route of administration. CONCLUSIONS: The findings of this investigation reveal that topically administered moxifloxacin 0.5% can achieve relatively high aqueous concentrations. Although aqueous moxifloxacin levels achieved through the use of a collagen shield delivery device are lower, there are several advantages to this route of delivery that make it appealing in the immediate postoperative period. Future studies will be needed to precisely define the role of fourth-generation fluoroquinolones and presoaked collagen shields in the prophylaxis or management of intraocular infections

Forming a Consensus: Data and Guidance for Physicians Treating Diabetic Macular Edema

The diabetic macular edema (DME) treatment paradigm has evolved as the understanding of the disease pathology has grown. Since 2012, four pharmacotherapies have been approved by the U.S. Food and Drug Administration for the treatment of DME. First-line treatment of DME with anti-vascular endothelial growth factor [VEGF] agents has become the gold standard; however, an appreciable percentage of patients do not respond to anti-VEGF therapies. In patients who inadequately respond to anti-VEGF therapies, the underlying disease pathology may be mediated by a multitude of growth factors and inflammatory cytokines. For these patients, corticosteroids are an attractive treatment option because they not only downregulate VEGF, but also an array of cytokines. The phase 3 MEAD and FAME trials demonstrated significant visual acuity improvements associated with dexamethasone and fluocinolone acetonide, respectively, in patients with DME; however, class-specific adverse events, including increased intraocular pressure and cataract development, must be considered before use. A panel of experts gathered during the 2015 annual meeting of the American Academy of Ophthalmology for a roundtable discussion focused on patient selection and adverse event management associated with the use of the 0.19 mg fluocinolone acetonide intravitreal implant