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Purpose: To evaluate the efficacy, effect profile, and safety of dexamethasone implant on diabetic macular edema (DME) in a real-life setting, further comparing results by DME duration, previous treatment status, and diabetic control., Design: A multicenter, retrospective cohort of 340 DME eyes of 287 patients from 25 clinical sites from 8 countries., Methods: Data were analyzed in 2 perspectives: per injection, in which all measurements were grouped and baseline was defined as the day of injection, and thus the pharmacodynamics of single injections could be assessed; and injection series, defined as 2 or more injections with 3 to 6 months between injections analyzing the outcome 3 to 6 months after the last injection., Main Outcome Measures: Primary outcome was improvement of 15 or more letters in best-corrected visual acuity (BCVA) from baseline. Secondary outcomes included improvement of 10 letters or more in BCVA, change in central macular thickness (CMT), and time to maximum improvement and safety., Results: Overall, 762 injections were administered to 340 eyes of 287 patients. Injection series analysis included 171 series in 171 eyes of 150 patients, for a total of 444 injections, with a mean follow-up of 1.7±0.8 years. Of the 762 injections analyzed per injection, 22.7% achieved a 15-letter or more improvement, and 37.8% achieved a 10-letter or more improvement. Mean time to peak improvement was 81.9±39.7 days. Mean maximum change in CMT was -174±171 μm. Overall, 7.6% lost 15 or more letters. More eyes with early DME gained 10 or more letters and fewer eyes lost 10 or more letters compared with eyes with late DME (47.4% vs. 33.9% [P = 0.001] and 8.2% vs. 13.5% [P = 0.029], respectively). Patients with controlled diabetes showed greater CMT reduction (P = 0.0002). A higher percentage of treatment-naive patients gained 10 or 15 letter or more in BCVA (P = 0.001 and P = 0.006, respectively). Intraocular pressure elevation of more than 25 mmHg was found following 7.9% of injections; no endophthalmitis was reported., Conclusions: Dexamethasone implant is an effective and safe treatment for DME. Peak improvement was achieved 3 months after injection and dissipated thereafter. Clinicians and providers may consider shortening treatment intervals., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate disorganization of retinal inner layers (DRIL) as a biomarker in eyes with diabetic macular oedema (DME) treated by intravitreal dexamethasone (DEX) implant., Methods: Multicentre, retrospective study including eyes with DME treated with DEX implant and follow-up of 12 months after the first injection. OCT scans were evaluated for the presence of DRIL and other structural features. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline and at 2, 4, 6 and 12 months after treatment. Correlation between DRIL at baseline and outcomes after DEX treatment and the change in DRIL were analysed., Results: A total of 177 eyes (177 patients; naïve, n = 131; refractory, n = 46) were included. Patients without DRIL at baseline gained significantly more vision and enjoyed greater reduction in CST over 12 months (both p = 0.03). DRIL at the boundary between the ganglion cell-inner plexiform complex and inner nuclear layer improved in 48/64 eyes (75%, p < 0.001), while DRIL between the inner nuclear layer and outer plexiform layer improved in 27/77 eyes (35%, p = 0.004)., Conclusions: This is the first study to show that DEX implant has the potential to ameliorate DRIL. Patients without DRIL at baseline have a favourable outcome. DRIL may serve a robust biomarker in DME treated by DEX implant., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Delivery of pharmaceuticals to the posterior segment presents challenges that arise from the anatomy and clearance pharmacokinetics of the eye. Systemic and several local administration options [topical, periocular, intravitreal (IVT) and subretinal] are in clinical use, each with a unique benefit to risk profile shaped by factors including the administered agent, frequency of dosing, achievable pharmaceutical concentrations within posterior segment structures versus elsewhere in the eye or the body, invasiveness of the procedure and the inherent challenges with some administration methods. The use of the suprachoroidal space (SCS), which is the region between the sclera and the choroid, is being explored as a potential approach to target pharmacotherapies to the posterior segment via a minimally invasive injection procedure. Preclinical data on agents such as vascular endothelial growth factor inhibitors and triamcinolone acetonide (TA) indicate that administration via suprachoroidal injection results in more posterior distribution of the pharmacologic agent, with higher exposure to the sclera, choroid, retinal pigment epithelium cells and retina, and lesser exposure to the anterior segment, than observed with IVT administration. Based in part on these findings, clinical trials have explored the efficacy and safety of suprachoroidal administration of pharmacologic therapies in conditions affecting the posterior segment. Data on a proprietary formulation of TA administered by suprachoroidal injection show improvement in anatomic and visual outcomes in subjects with noninfectious uveitis, with the potential to mitigate the known risks of cataract and increased intraocular pressure (IOP) associated with the use of intraocular corticosteroids. Suprachoroidal administration appears to be a promising treatment modality and is also in the early stages of investigation for other possible applications, such as injection of antiglaucoma agents into the anterior SCS for long-lasting control of elevated IOP, and as a mode of delivery for gene- or cell-based therapies for retinal disorders., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To characterize cat-scratch disease (CSD) ocular manifestations and visual outcome and evaluate the effect of systemic antibiotics and corticosteroids on final visual acuity (VA)., Methods: Multicentre retrospective cohort study. Medical records of 86 patients with ocular disease (107 eyes) of 3222 patients identified in a national CSD surveillance study were reviewed., Results: Mean age was 35.1 ± 14.2 years. Median follow-up was 20 weeks (range 1-806 weeks). Of 94/107 (88%) eyes with swollen disc, 60 (64%) had neuroretinitis at presentation, 14 (15%) developed neuroretinitis during follow-up, and 20 (21%) were diagnosed with inflammatory disc oedema. Optic nerve head lesion, uveitis, optic neuropathy and retinal vessel occlusion were found in 43 (40%), 38 (36%), 34 (33%) and 8 (7%) eyes, respectively. Good VA (better than 20/40), moderate vision loss (20/40-20/200) and severe vision loss (worse than 20/200) were found in 26/79 (33%), 35/79 (44%) and 18/79 (23%) eyes at baseline and in 63/79 (80%), 11/79 (14%) and 5/79 (6%) eyes at final follow-up, respectively (p < 0.001). Significant VA improvement (defined as improvement of ≥3 Snellen lines at final follow-up compared to baseline) occurred in 12/24 (50%) eyes treated with antibiotics compared with 14/16 (88%) eyes treated with antibiotics and corticosteroids (p = 0.02). Multivariate logistic regression was suggestive of the same association (odds ratio 7.0; 95% CI 1.3-37.7; p = 0.024)., Conclusion: Optic nerve head lesion is a common and unique manifestation of ocular CSD. Most patients improved and had final good VA. Combined antibiotics and corticosteroid treatment was associated with a better visual outcome., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the safety and efficacy of 1.5% dexamethasone nanoparticle (DexNP) drops in eyes with non-infectious uveitic macular oedema and vitritis., Methods: In a prospective pilot study, DexNP drops were administered four times a day for 4 weeks followed by drops tapering over a period of another 4 weeks. Follow-up time was 12 weeks., Results: Five eyes with macular oedema and three eyes with vitritis were included in the study. Best corrected visual acuity (BCVA) significantly improved from a median of 0.2 logMAR to a median of 0.15 logMAR at 4 weeks' time (p < 0.05). Median BCVA was 0.175 logMAR and 0.2 logMAR, at week 8 and 12, respectively (p > 0.05). Macular oedema significantly improved at all time-points as compared to baseline (p < 0.05) and resolved in all eyes during follow-up. One eye had macular oedema relapse at week 12. Vitritis improved in all eyes and resolved completely in two eyes. One eye had intraocular pressure (IOP) elevation which was well controlled with topical antihypertensive treatment, and one eye had cataract progression., Conclusion: This short pilot study demonstrates favourable effect of 1.5% DexNP eye drops on eyes with non-infectious uveitic macular oedema and vitritis. Further comparative long-term studies are warranted to assess this effect., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To examine the effect of an intravitreal dexamethasone drug delivery system (DEX-DDS) in the treatment of persistent cystoid macular edema (CME) of different etiologies., Methods: Thirty-seven eyes with persistent CME were treated with DEX-DDS and analyzed for changes in best-corrected visual acuity (BCVA) and optical coherence tomography. Eyes were categorized into three groups: diabetic macular edema (DME, n = 14), vein occlusion (n = 15) and uveitis (n = 7)., Results: The mean follow-up was 22 ± 6.9 weeks. BCVA improved from 0.62 ± 0.38 to 0.35 ± 0.29 logMAR (p < 0.0001). Central macular thickness decreased by 184 ± 246 µm from baseline (p < 0.0001). In eyes where CME resolved and recurred, the average CME-free period was 11 weeks. The uveitis group showed faster CME resolution (2 weeks) and a longer CME-free period (20 weeks). Similar efficacy was shown for repeat DEX-DDS injections. The safety profile was good., Conclusion: DEX-DDS is beneficial in the treatment of persistent CME. In cases of uveitis, CME resolution is rapid, resulting in the longest effect duration, when compared with other CME etiologies., (© 2014 S. Karger AG, Basel.)

Purpose: To report the long-term outcome of an intravitreal dexamethasone drug delivery system (DEX-DDS) injection for noninfectious uveitic macular edema., Methods: This was a retrospective study of 8 eyes (7 patients)., Results: The mean follow-up time was 17.3 months. Macular edema resolved in all eyes at 3.9 weeks (range 1-6.9) postinjection. The central point thickness improved from 612 ± 143 to 250 ± 55 µm (p < 0.05). The mean best corrected visual acuity improved by 0.25 logMAR (p < 0.05) at 3.9 weeks (range 1-6.9) postinjection. In 5 eyes, macular edema did not recur after a mean follow-up of 14.5 months. In 3 eyes, macular edema relapsed after 4.7 months (range 3.6-6.3) and resolved again following further injections. Two eyes developed intraocular pressure elevation, which was well controlled with topical treatment., Conclusions: Intravitreal DEX-DDS injections resulted in resolution of macular edema and visual acuity improvement. Some eyes required repeated injections, but most eyes achieved long-term resolution. No significant complications were noticed., (© 2014 S. Karger AG, Basel.)

Purpose: To report the outcome of a single intravitreal triamcinolone acetonide (IVTA) injection as an adjunctive treatment with systemic medication for refractory uveitic cystoid macular edema (CME)., Methods: This was a retrospective, noncomparative, interventional case series. Medical records of 25 patients (35 eyes) with quiescent uveitic CME who were treated with oral immunosuppressive therapy and underwent 4 mg/0.1 mL IVTA injection were reviewed. Data was collected 6 months post-injection and included details of uveitis, best-corrected visual acuity (BCVA), CME, systemic therapy required, and potential complications of IVTA injection., Results: Thirty eyes (85%) responded with improvement in vision. The mean BCVA improvement was 0.33 (from 0.67 to 0.34 logarithm of the minimum angle of resolution; Snellen equivalent, between 2 and 3 lines) (p<0.001), at a mean time of 6.2 weeks (range 2-16). Resolution of CME was achieved in 31 (88%) of the treated eyes. Following initial response to IVTA, CME relapsed in 8 eyes (26%) after a mean time of 4.2 months (range 2.5-5.5). The dosage of oral corticosteroids and/or second-line immunosuppressive agents was able to be reduced or stopped in 22 patients, 29 of 35 eyes (82.8%). The most common adverse effect was increased intraocular pressure, in 17 (49%) of the treated eyes. Steroid-induced cataract was observed in 6 eyes (17%)., Conclusions: Intravitreal triamcinolone acetonide appears to be an effective supplementary tool in the management of CME refractory to systemic immunosuppressive therapy. Retreatment might be required in some and may be associated with elevated intraocular pressure and cataract.

Purpose: To report the outcome of orbital floor corticosteroid injection (OFCI) in the management of uveitis in children., Methods:   A retrospective noncomparative interventional case series. The medical records of 15 consecutive children (19 eyes) with various forms of uveitis treated with OFCI of 40 mg/ml methylprednisolone acetate or a combination of 20 mg/0.5 ml Triamcinolone and 2 mg/0.5 ml dexamethasone were reviewed. Data were collected 6 months postinjection and included details of uveitis, best corrected visual acuity (BCVA), ocular inflammation, systemic therapy required and potential complications of OFCI., Results: The mean BCVA improvement was 0.18 logarithm of the minimum angle of resolution (p < 0.001), at a mean of 6 weeks (range, 4-20). Fourteen eyes (74%) had significant improvement in inflammation, 4-7 weeks post-OFCI, with a median of 4 weeks. Anterior uveitis was treated effectively in all eyes, vitritis resolved in all but one case and resolution of cystoid macular oedema was achieved in six eyes (55%). Uveitis relapsed in seven eyes (50%) after a median time of 4 months (range, 2-5 months). Four eyes (21%) underwent more than one injection. The dosage of immunosuppressive systemic therapy was reduced or able to be stopped in three patients (50%). Steroid-induced cataract was observed in four eyes (21%), 5 months post-OFCI. One patient developed cushingoid features 6 weeks post his second OFCI., Conclusion: Corticosteroid orbital floor injections resulted in control of active uveitis and visual acuity improvement in most children. However, the effect might be transient and induce cataract formation., (© 2010 The Authors. Acta Ophthalmologica © 2010 Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To compare the management and outcome of raised intraocular pressure (IOP) in uveitis patients with a corticosteroid hypertensive response and those who are noncorticosteroid responders and to determine the impact of intraocular corticosteroid use on IOP in uveitic eyes., Design: Retrospective study., Methods: Eight hundred and ninety-one uveitis patients were observed in a specialized clinic over 3 months. The main outcome measures were frequency, characterization, management, and outcome of uveitis-related ocular hypertension and glaucoma., Results: Of 891 patients with uveitis, 191 (275 eyes) had IOP elevation (21.4%). Of these, 95 (34.5%) eyes had glaucoma. IOP elevation attributed to corticosteroid-response (61.1%) was controlled more easily than that resulting from other causes (38.9%), requiring fewer eye drops (mean, 2.06 vs 2.52; P = .009) and less filtration surgery (8.9% vs 22.4%). Among eyes with uveitis and raised IOP, elevated IOP developed in 18 eyes (6.5%) after intravitreal triamcinolone, including 64.7% to 30 to 39 mm Hg and 35.3% to 40 mm Hg or more. Prostaglandin analogs were used in 49.2% of 246 eyes; no increase in inflammation was seen in these eyes., Conclusions: In this tertiary center series, most instances of raised IOP were attributable to corticosteroid response. Raised IOP induced by corticosteroid response was controlled more easily and less often resulted in optic nerve or visual field changes of glaucoma. Although intravitreous triamcinolone was associated with substantial risk of corticosteroid-response IOP elevation, all cases were controlled medically without experiencing glaucomatous injury. Prostaglandin-induced uveitis was not observed despite extensive use of prostaglandin IOP-lowering agents.