• Anti-vascular endothelial growth factor therapy
• Diabetic retinopathy
• Intravitreal gene therapy
• Intravitreal injections
• Neovascular age-related macular degeneration

• Humans
• Intravitreal Injections/economics
• Angiogenesis Inhibitors/administration & dosage
• Angiogenesis Inhibitors/adverse effects
• Vascular Endothelial Growth Factor A/antagonists & inhibitors
• Genetic Therapy
• Diabetic Retinopathy/drug therapy
• Macular Edema/drug therapy
• Cost-Benefit Analysis
• Macular Degeneration/drug therapy
• Geographic Atrophy/drug therapy

• Paracelsus Medical University

• Corticosteroids
• Dexamethasone
• Lipid nanoparticles
• Nanoparticles
• Ocular drug delivery
• Polymeric nanoparticles
• Triamcinolone

• Humans
• Adrenal Cortex Hormones/administration & dosage
• Adrenal Cortex Hormones/therapeutic use
• Drug Delivery Systems/methods
• Nanotechnology/methods
• Administration, Ophthalmic
• Nanoparticles/chemistry
• Animals
• Nanoparticle Drug Delivery System/chemistry

• Adjuvants
• Anti-vascular endothelial growth factor
• Diabetic retinopathy
• Intravitreal injections
• Outcomes
• Vitrectomy

• CME
• OCT
• Retina
• cystoid macular edema
• intravitreal injections
• macular edema
• optical coherence tomography
• retinal detachment
• silicone oil

• provided

• Diabetic macular edema
• Retinal vein occlusion
• Triamcinolone acetonide

• Humans
• Macular Edema/drug therapy
• Macular Edema/etiology
• Macular Edema/diagnosis
• Retinal Vein Occlusion/complications
• Retinal Vein Occlusion/drug therapy
• Retinal Vein Occlusion/diagnosis
• Intravitreal Injections
• Diabetic Retinopathy/drug therapy
• Diabetic Retinopathy/diagnosis
• Diabetic Retinopathy/complications
• Triamcinolone Acetonide/administration & dosage
• Glucocorticoids/administration & dosage
• Visual Acuity
• Tomography, Optical Coherence/methods
• Treatment Outcome
• Randomized Controlled Trials as Topic

• intravitreal injections
• liposomes
• nano delivery systems
• posterior segment disease
• retinal diseases
• triamcinolone acetonide

• Cataract
• Intravitreal injection
• Macular edema
• Phacoemulsification
• Steroid
• Uveitis

The present study evaluated the effectiveness of suprachoroidal injection of triamcinolone acetonide (TA) in resistant diabetic macular edema (DME) using a modified microneedle.

This is a prospective nonrandomized interventional study that was conducted on 55 eyes of 39 patients with centrally involving DME resistant to previous antivascular endotheli qal growth factor (VEGF) agents. All patients received suprachoroidal injection of triamcinolone acetonide 4 mg/0.1 mL by a modified specialized microneedle.

The mean central macular thickness (CMT) decreased sign ificantly from 478.7±170.2 µm before injection to 230.2±47.4 µm after 12 months with p-value <0.001. Significant improvement of the mean best corrected visual acuity (BCVA) from 1.193±0.2 by logMAR at the baseline to 0.76±0.3 by logMAR was achieved after 12 months with p-value <0.001. The IOP increased significantly at one month after injection and returned to the baseline value at the third month. Eyes with more baseline CMT and worse baseline BCVA achieved worse final BCVA 12 months after injection. Eyes with inner segment/outer segment (IS/OS) disruption and neurosensory detachment (NSD) showed worse final visual outcomes. IS/OS segment disruption, NSD and baseline BCVA were the main independent predictors of the final BCVA.

Suprachoroidal injection of TA using this new modified microneedle resulted in marked anatomical and functional results in cases of DME resistant to previous anti-VEGF drugs with no serious ocular or systemic side effects. The study was prospectively registered with clinical trial.gov ID (NCT04690608) in 27–12-2020.

• No funding was received

The use of steroids to treat macular edema (ME) is a research hotspot in ophthalmology. We utilized CiteSpace and VOSviewer software to evaluate the Web of Science Core Collection publications and to build visualizing maps to describe the research progress in this topic. There were 3,252 publications for three decades during 1988–2021. The number of studies was low during the first 14 years but has risen consistently in the following two decades. The average publications per year were only 4.8 during 1988–2002, which jumped to 113 per year during 2003–2012, and 227 per year during 2013–2021. These publications came from 83 countries/regions, with the United States, Germany, and Italy leading positions. Most studies were published in Investigative Ophthalmology Visual Science, and Ophthalmology was the most cited journal. We found 9,993 authors, with Bandello F having the most publications and Jonas JB being the most frequently co-cited. According to our research, the most popular keyword is triamcinolone acetonide (TA). Macular edema, diabetic macular edema (DME), retinal vein occlusion (RVO), dexamethasone (DEX), fluocinolone acetonide (FA), and some other keywords were commonly studied in this field. In conclusion, the bibliometric analysis provides a comprehensive overview of steroid hotspots and developmental tendencies in the macular edema study. While anti-VEGF therapy is the first-line treatment for DME and RVO-induced macular edema, steroids implant is a valid option for these DME patients not responding to anti-VEGF therapy and non-DME patients with macular edema. Combined therapy with anti-VEGF and steroid agents is vital for future research.

• VOSviewer
• bibliometric study
• citespace
• intravitreal injection
• macular edema
• steroids

• anti-VEGF
• corticosteroids
• nonsteroidal anti-inflammatory drugs
• postsurgical macular edema

To compare the effect of adding a corticosteroid or switching to another anti-VEGF treatment in patients with exudative age-related macular degeneration (eAMD) with persisting intraretinal fluid on anti-VEGF monotherapy.

This retrospective, interventional case series involved 43 pseudophakic eyes with eAMD and persistent intraretinal fluid on anti-VEGF treatment that switched treatment to a combination of Ozurdex^® or Triamcinolone and anti-VEGF therapy (group 1) or to another anti-VEGF agent (group 2). The number of injections, time to re-injection, change in central retinal thickness (CRT), and best-corrected visual acuity (BCVA) from 12 months prior to 12 months after switch to third-line therapy were defined as primary outcomes.

Whereas the treatment demand was reduced (from 8.8±2.2 to 4.6±2.9 injections; p=0.001) and the re-injection interval extended in group 1 (from 1.5±0.4 months to 4.4±3.8 months; p=0.001), these parameters did not change in group 2 (7.4±1.6 to 7.3±2.2; p=0.90 and 1.7±0.3 months to 1.9±0.8 months; p=0.75). Mean CRT decreased from 455.7±30.1 and 427.6±36.0µm (groups 1 and 2, respectively) to 359.1±38.2 and 303.1±44.4µm (intergroup p=0.03). The mean baseline BCVA of 62.6±3.8 letters (group 1) and 63.0±1.9 letters (group 2) remained stable under therapy in both groups (intergroup p=0.67).

In eyes with eAMD with persistent intraretinal fluid on anti-VEGF monotherapy despite frequent re-injections, corticosteroids achieved a similar functional and morphological outcome over 12 months as switching to another anti-VEGF therapy, but with a reduced injection burden. In selected cases, corticosteroid treatment may thus be an option for third-line therapy in refractory exudative AMD.

• Ozurdex
• aflibercept
• dexamethasone intravitreal implant
• exudative age-related macular degeneration
• ranibizumab
• triamcinolone

• Anti-inflammatory therapies
• Corticosteroids
• Diabetic macular oedema
• Diabetic retinopathy
• Inflammation
• NSAIDs

• Angiogenesis Inhibitors/administration & dosage
• Anti-Inflammatory Agents/administration & dosage
• Diabetic Angiopathies/complications
• Diabetic Angiopathies/therapy
• Diabetic Retinopathy/etiology
• Diabetic Retinopathy/therapy
• Drug Therapy, Combination/methods
• Drug Therapy, Combination/trends
• Glucocorticoids/administration & dosage
• Humans
• Inflammation/complications
• Inflammation/therapy
• Intravitreal Injections

This study aims to report a case of rapid progression of cataract to mature stage after intravitreal dexamethasone implantation for macular edema due to branch retinal vein occlusion.

A 59-year-old Korean male with complaints of sudden metamorphopsia and reduced visual acuity for three days in the left eye was referred to our clinic. Ophthalmological investigations included fundus photography, fluorescein angiography, and optical coherence tomography. In the left eye, branch retinal vein occlusion with macular edema was observed. We performed intravitreal dexamethasone implantation in the left eye three times within a period of one year. One week after the third intravitreal dexamethasone implantation, grade 1 posterior subcapsular opacity and raised intraocular pressure were observed in the left eye. Three weeks later, mature cataract was observed in the left eye. We performed cataract surgery along with intravitreal ranibizumab injection in the left eye. The procedure was uneventful, and the visual acuity improved postoperatively.

Posterior subcapsular cataract developed due to intravitreal dexamethasone implantation can progress rapidly to mature stage. Therefore, short-term follow-up examinations may be necessary for early diagnosis and treatment of this complication.

• Intravitreal dexamethasone implant
• Macular edema
• Mature cataract
• Ozurdex
• Retinal vein occlusion

• China
• Diabetic Retinopathy/drug therapy
• Drugs, Chinese Herbal/therapeutic use
• Ginsenosides/therapeutic use
• Humans
• Isoflavones/therapeutic use
• Microaneurysm/prevention & control
• Phytotherapy/methods
• Plants, Medicinal
• Pyrazines/therapeutic use
• Randomized Controlled Trials as Topic
• Retinal Hemorrhage/prevention & control
• Ruscus/chemistry
• Saponins/therapeutic use
• Vasodilator Agents/therapeutic use
• Visual Acuity/drug effects

• cystoid macular oedema
• diclofenac
• uveitis

The visual outcome of uveitic cataract surgery depends on the underlying uveitic diagnosis, the presence of vision-limiting pathology and perioperative optimization of disease control. A comprehensive preoperative ophthalmic assessment for the presence of concomitant ocular pathology, with particular emphasis on macula and optic nerve involvement, is essential to determine which patients will benefit from improved vision after cataract surgery. Meticulous examination in conjunction with adjunct investigations can help in preoperative surgical planning and in determining the need for combined or staged procedures. The eye should be quiescent for a minimum of 3 months before cataract surgery. Perioperative corticosteroid prophylaxis is important to reduce the risk of cystoid macular edema and recurrence of the uveitis. Antimicrobial prophylaxis may also reduce the risk of reactivation in eyes with infectious uveitis. Uveitic cataracts may be surgically demanding due to the presence of synechiae, membranes, and pupil abnormalities that limit access to the cataract. This can be overcome by manual stretching, multiple sphincterotomies or mechanical dilation with pupil dilation devices. In patients <2 years of age and in eyes where the inflammation is poorly controlled, intraocular lens implantation should be deferred. Intensive local and/or oral steroid prophylaxis should be given postoperatively if indicated. Patients must be monitored closely for disease recurrence, excessive inflammation, raised intraocular pressure, hypotony, and other complications. Complications must be treated aggressively to improve visual rehabilitation. With proper patient selection, improved surgical techniques and optimization of peri- and post-operative care, patients with uveitic cataracts can achieve good visual outcomes.

Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H₂O₂). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis.

There is increasing use of the vitreous cavity as a reservoir for drug delivery. We study the intraocular migration and distribution of triamcinolone acetonide (TA) after injection into silicone oil tamponade agent during and after vitrectomy surgery ex vivo (pig eye) and in vitro (glass bottle). For ex vivo assessment, intraocular migration of TA was imaged using real-time FLASH MRI scans and high-resolution T2W imaging and the in vitro model was monitored continuously with a video camera. Results of the ex vivo experiment showed that the TA droplet sank to the interface of silicone oil and aqueous almost immediately after injection and remained inside the silicone oil bubble for as long as 16 minutes. The in vitro results showed that, after the shrinkage of the droplet, TA gradually precipitated leaving only a lump of whitish crystalline residue inside the droplet for about 100 minutes. TA then quickly broke the interface and dispersed into the underlying aqueous within 15 seconds, which may result in a momentary increase of local TA concentration in the aqueous portion and potentially toxic to the retina. Our study suggests that silicone oil may not be a good candidate as a drug reservoir for drugs like TA.

• Solid lipid nanoparticles
• drug delivery
• eye
• nanostructured lipid carrier

Macular edema such as diabetic macular edema (DME) and diabetic retinopathy are devastating back-of-the-eye retinal diseases leading to loss of vision. This area is receiving considerable medical attention. Posterior ocular diseases are challenging to treat due to complex ocular physiology and barrier properties. Major ocular barriers are static (corneal epithelium, corneal stroma, and blood-aqueous barrier) and dynamic barriers (blood-retinal barrier, conjunctival blood flow, lymph flow, and tear drainage). Moreover, metabolic barriers impede posterior ocular drug delivery and treatment. To overcome such barriers and treat back-of-the-eye diseases, several strategies have been recently developed which include vitreal drainage, laser photocoagulation and treatment with biologics and/or small molecule drugs. In this article, we have provided an overview of several emerging novel strategies including nanotechnology based drug delivery approach for posterior ocular drug delivery and treatment with an emphasis on DME.

• Diabetic macular edema
• Photocoagulation
• Retinopathy
• Biologics
• Vitrectomy
• Corticosteroids
• Nanoformulations
• Laser

Patients with diabetic macular edema (DME), a chronic, vision-limiting condition, may be insufficiently responsive to standard-of-care anti-vascular endothelial growth factor (VEGF) and/or laser therapies. One approved treatment for such patients is 0.2 μg/day fluocinolone acetonide (FAc) sustained-release implant; however, data are limited for treatment strategies in patients with bilateral chronic DME insufficiently responsive to standard-of-care therapies.

Six pseudophakic patients with bilateral, chronic DME previously treated with laser and anti-VEGF therapy (and intravitreal triamcinolone acetonide in 10 eyes) were retrospectively investigated for visual and anatomical outcomes, 6 months post-0.2 μg/day FAc implant in both eyes.

At baseline, the mean best corrected visual acuity (BCVA) was approximately 6/38 or 43 [standard deviation (SD) ±17.4] Early Treatment Diabetic Retinopathy Study (ETDRS) letters; mean central retinal thickness (CRT) was 648 μm (SD ±160). Mean change in BCVA was +10 letters (SD ±12.2 letters), with 4/12 eyes maintaining or achieving driving vision (≥70 letters) and 3/12 eyes having unchanged BCVA. CRT was reduced 6 months after 0.2 μg/day FAc implant in 11/12 eyes. The mean intraocular pressure (IOP) was 16.1 mmHg [mean change of 1.1 mmHg (SD ±3.6)].

In a real-world setting, 0.2 μg/day FAc implant in both eyes was a feasible, effective choice for patients with severe bilateral DME, without notable increases in IOP.

Publication charges were funded by Alimera Sciences Ltd. Medical writing assistance for this study was provided by QXV Communications and funded by Alimera Sciences Ltd.

The online version of this article (doi:10.1007/s40123-016-0045-7) contains supplementary material, which is available to authorized users.

• Bilateral diabetic macular edema
• Central retinal thickness
• Fluocinolone acetonide
• Optical coherence tomography
• Visual acuity

Iluvien^® is a novel, nonbiodegradable, sustained-release drug delivery system (0.2 μg/d fluocinolone acetonide [FAc]) indicated in Europe for the treatment of vision impairment associated with chronic diabetic macular edema (DME), considered insufficiently responsive to available therapies.

To evaluate the safety and efficacy of 190-μg FAc implant in patients with chronic DME refractory to other medical treatment options in a clinical setting.

Retrospective registry data were collected by using standard case report forms (CRFs). Prior to intravitreal injection of the FAc implant, all patients were treated either with a vascular endothelial growth factor (VEGF) antagonist and/or a steroid (triamcinolone, dexamethasone implant). Patients were excluded from receiving FAc if they had a known history of elevated intraocular pressure (IOP) following corticosteroid therapy, glaucoma, ocular hypertension, or any contraindications cited in the summary of product characteristics. Best-corrected visual acuity (BCVA) was the main study parameter. Central fovea thickness (CFT) and IOP were measured concurrently. These parameters were recorded prior to and after the injection of the 190-μg FAc implant (between 1 week and 9 months). Injections were performed between May 2013 and March 2014.

Fifteen eyes from ten patients were treated. Thirteen eyes (nine patients) were pseudophakic, and seven eyes (five patients) were vitrectomized prior to receiving therapy. BCVA improved in eleven eyes (73.3%), remained unchanged in two eyes (13.3%), and decreased slightly in two eyes (13.3%) at the last follow-up visit versus baseline levels. IOP increased in two patients and was controlled using fixed-combination of IOP-lowering eyedrops or sectorial cyclocryotherapy (n=1).

The 190-μg FAc implant was efficacious and showed a favorable benefit-to-risk profile in the patient population with chronic DME of this case series that were refractory to other therapies. The longer-term efficacy and safety in a real-life setting is still being assessed in this center. FAc may offer an important treatment option for patients with chronic DME refractory to other treatment options.

• best-corrected visual acuity
• corticosteroid
• diabetic macular edema
• fluocinolone acetonide
• intravitreal implant

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors/administration & dosage
• Antibodies, Monoclonal, Humanized/administration & dosage
• Eye Diseases/diagnostic imaging
• Eye Diseases/etiology
• Female
• Humans
• Intraoperative Complications
• Intravitreal Injections/adverse effects
• Macular Degeneration/drug therapy
• Macular Edema/drug therapy
• Male
• Microscopy, Acoustic
• Middle Aged
• Prospective Studies
• Ranibizumab
• Retinal Vein Occlusion/drug therapy
• Sclera
• Vascular Endothelial Growth Factor A/antagonists & inhibitors
• Vitreous Body/diagnostic imaging
• Vitreous Body/pathology

• Cell Line
• Cell Survival/drug effects
• Dendrimers/chemical synthesis
• Dendrimers/chemistry
• Dendrimers/toxicity
• Epithelial Cells/cytology
• Epithelial Cells/metabolism
• Genetic Vectors/chemistry
• Genetic Vectors/metabolism
• Genetic Vectors/toxicity
• Humans
• Microscopy, Fluorescence
• Polyamines/chemistry
• Polyethylene Glycols/chemistry
• Retina/cytology
• Transfection
• Triamcinolone Acetonide/chemistry

• P30 EY001765 NEI NIH HHS
• R01 EB018306 NIBIB NIH HHS
• R01 EY025304 NEI NIH HHS
• 1R01EB018306-01 NIBIB NIH HHS

• Inflammation
• Retina
• Treatment Medical

• central retinal vein occlusion
• choroidal neovascular membrane
• diabetic macular edema
• intravitreal triamcinolone acetonide
• ocular blood flow

Our objective was to investigate the efficacy and safety of dexa methasone (DEX) implant for the treatment of pseudophakic cystoid macular edema (PCME) in diabetic patients.

This was a prospective, non-randomized, interventional case series of 43 participants. Eighteen patients were enrolled in the DEX implant group and 25 were enrolled in an intravitreal triamcinolone acetonide (IVTA) group.

The primary efficacy measurement was the percentage of patients who gained improvements of more than ten letters in best corrected visual acuity (BCVA) during 6 months of follow-up. Other efficacy measurements included change in BCVA, change in central macular thickness (CMT), and number of retreatments. The primary safety evaluation was the percentage of patients with intraocular hypertension and variation in intraocular pressure (IOP) during 6 months of follow-up. Other adverse events, such as conjunctival hemorrhage, eye pain, secondary infection, endophthalmitis, noninfectious inflammation, retinal detachment, and implant migration, were also recorded during follow-up.

At month 1, we observed that the percentage of patients gaining improvement of more than ten letters was similar in both groups (P=0.625). As patients in the IVTA group were retreated several times, this effect persisted throughout the study (P=0.941 at month 2, P=0.553 at month 3, P=0.856 at month 6). Variations in CMT were noticed at week 1 and reached their maximum at month 1. No significant difference was found between the two groups (P=0.831 at week 1, P=0.783 at month 1). At month 1, the variation in IOP reached its maximum in the DEX implant group and then decreased slightly. However, in the IVTA group, it increased continuously throughout the study. Conjunctival hemorrhage and eye pain were found in both groups, but both were rated as mild in severity, and no significant difference was found (P=0.184, P=0.766, respectively).

Both IVTA and DEX implants could effectively restore visual function and recover morphological change in diabetic patients with PCME for at least 6 months, but repeated intravitreal injection was required in the IVTA group. DEX implant is well tolerated. We suggest that intravitreal injection of DEX implant is a promising new therapeutic option for diabetic patients with PCME.

• corticosteroid
• dexamethasone implant
• diabetic retinopathy
• inflammation
• intravitreal triamcinolone acetonide
• pseudophakic cystoid macular edema

• anti-vascular endothelial growth factor
• corticosteroids
• non-steroidal anti-inflammatory agents
• pars plana vitrectomy
• pseudophakic cystoid macular edema

• Diagnostic tests/Investigation
• Immunology
• Infection
• Inflammation
• Treatment Surgery

Uveitic macular edema is the major cause of reduced vision in eyes with uveitis.

To assess the effectiveness of interventions in the treatment of uveitic macular edema.

Cochrane Central Register of Controlled Trials, Medline, and Embase. There were no language or data restrictions in the search for trials. The databases were last searched on December 1, 2011. Reference lists of included trials were searched. Archives of Ophthalmology, Ophthalmology, Retina, the British Journal of Ophthalmology, and the New England Journal of Medicine were searched for clinical trials and reviews.

Participants of any age and sex with any type of uveitic macular edema were included. Early, chronic, refractory, or secondary uveitic macular edema were included. We included trials that compared any interventions of any dose and duration, including comparison with another treatment, sham treatment, or no treatment.

Best-corrected visual acuity and central macular thickness were the primary outcome measures. Secondary outcome data including adverse effects were collected.

More results from randomized controlled trials with long follow-up periods are needed for interventions for uveitic macular edema to assist in determining the overall long-term benefit of different treatments. The only intervention with sufficiently robust randomized controlled trials for a meta-analysis was acetazolamide, which was shown to be ineffective in improving vision in eyes with uveitic macular edema, and is clinically now rarely used. Interventions showing promise in this disease include dexamethasone implants, immunomodulatory drugs and anti-vascular endothelial growth-factor agents. When macular edema has become refractory after multiple interventions, pars plana vitrectomy could be considered. The disease pathophysiology is uncertain and the course of disease unpredictable. As there are no clear guidelines from the literature, interventions should be tailored to the individual patient.

• uveitic macular edema
• uveitis

• Animals
• Biomedical Research
• Humans
• Manuscripts as Topic
• Ophthalmology
• Review Literature as Topic
• Serial Publications/trends

• intravitreal injections
• medical treatment
• occlusion
• retina
• retinal vein