• Humans
• Kidney/drug effects
• Kidney/pathology
• Vascular Endothelial Growth Factors/antagonists & inhibitors

• Angiogenesis
• Diabetic retinopathy
• Dysregulation
• Homeostasis
• Hyperglycemia
• Hyperlipidemia
• Hypertension
• Inflammation
• Retinal glia
• Visual impairment

• Humans
• Palmitic Acid/therapeutic use
• Angiotensin II/therapeutic use
• Diabetic Retinopathy
• Neuroglia/pathology
• Hyperglycemia
• Glucose
• Hypertension
• Diabetes Mellitus

• R01 EY007533 NEI NIH HHS
• F32 DK116542 NIDDK NIH HHS
• K08 EY029006 NEI NIH HHS
• R01 EY023639 NEI NIH HHS
• R01 EY023397 NEI NIH HHS

• Diabetic macular edema
• betamethasone
• bromfenac
• central subfield thickness
• intraocular pressure

Diabetic retinopathy (DR), with increasing incidence, is the major cause of vision loss and blindness worldwide in working-age adults. Diabetic macular edema (DME) remains the main cause of vision impairment in diabetic patients, with its pathogenesis still not completely elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of DR and DME. Currently, intravitreal injection of anti-VEGF agents remains as the first-line therapy in DME treatment due to the superior anatomic and functional outcomes. However, some patients do not respond satisfactorily to anti-VEGF injections. More than 30% patients still exist with persistent DME even after regular intravitreal injection for at least 4 injections within 24 weeks, suggesting other pathogenic factors, beyond VEGF, might contribute to the pathogenesis of DME. Recent advances showed nearly all the retinal cells are involved in DR and DME, including breakdown of blood-retinal barrier (BRB), drainage dysfunction of Müller glia and retinal pigment epithelium (RPE), involvement of inflammation, oxidative stress, and neurodegeneration, all complicating the pathogenesis of DME. The profound understanding of the changes in proteomics and metabolomics helps improve the elucidation of the pathogenesis of DR and DME and leads to the identification of novel targets, biomarkers and potential therapeutic strategies for DME treatment. The present review aimed to summarize the current understanding of DME, the involved molecular mechanisms, and the changes in proteomics and metabolomics, thus to propose the potential therapeutic recommendations for personalized treatment of DME.

• diabetic macular oedema
• diabetic retinopathy
• eye drops
• ophthalmic treatment
• retinal disease
• topical treatment

Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the mainstay in the management of center-involving diabetic macular edema (CI-DME). Topical nonsteroidal anti-inflammatory drugs (NSAIDs) have been used to treat CI-DME as well. Whether there is any benefit of using both together has not been explored. The aim of this study was to compare visual acuity and OCT outcomes in patients with CI-DME who receive intravitreal anti-VEGF with and without topical NSAIDs in CI-DME.

This was A retrospective observational study in two centers in India. The study compared visual and OCT parameters of patients with CI-DME treated with intravitreal anti-VEGF monotherapy (group 1, N = 100) versus intravitreal anti-VEGF therapy with topical NSAIDs (group 2, N = 50) over 1-year follow-up. Continuous and categorical parameters were compared using parametric and nonparametric tests, respectively.

Over the 1-year follow-up, group 2 received more mean number of intravitreal injections (group 1: 2.26 ± 1.71 vs. group 2: 3.74 ± 2.42; P < 0.0001). There were no differences between the groups in visual acuity and OCT thickness at 1-year follow-up.

Combination therapy of topical NSAIDs with intravitreal anti-VEGF did not show any beneficial effects in terms of visual outcomes, reduction in central subfoveal thickness, or reduction in the mean number of injections in our study.

• Diabetic macular edema
• intravitreal anti-VEGF
• topical nonsteroidal anti-inflammatory drugs

• Age-related macular degeneration
• Diabetic retinopathy
• NSAIDs
• Retinal neurodegenerative diseases

• Humans
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Anti-Inflammatory Agents, Non-Steroidal/pharmacology
• Neurodegenerative Diseases/drug therapy
• Animals
• Retinal Diseases/drug therapy
• Macular Degeneration/drug therapy

• Diabetic macula oedema
• Panretinal photocoagulation
• Pregnancy
• Proliferative diabetic retinopathy
• Severe nonproliferative diabetic retinopathy
• Sight-threatening diabetic retinopathy

To evaluate the analgesic effect of topical 0.1% nepafenac solution during intravitreal Ozurdex injection.

This prospective, randomized, double-blind placebo-controlled study included 59 patients who were diagnosed with retinal vein occlusion or pseudophakic cystoid macular edema and were selected to receive intravitreal Ozurdex injection. The patients were divided into two groups. Group 1, consisting of 31 eyes of 31 patients, received topical 0.1% nepafenac with topical anesthesia (0.5% proparacaine HCl, Alcaine; Alcon, TX, USA), and group 2, consisting of 28 eyes of 28 patients, received placebo with topical anesthesia.

There were 14 (45.2%) men and 17 (54.8%) women in group 1 and 16 (57.1%) men and 12 (42.9%) women in group 2. The mean age of the subjects was 64.42 ± 5.51 years in group 1 and 62.32 ± 7.54 years in group 2. The median visual analog scale pain score was 2 (1–3) in group 1 and 4 (1–6) in group 2. The visual analog scale pain score was significantly lower in group 1 than in group 2 (p < 0.001).

Topical 0.1% nepafenac has an additive analgesic effect when combined with topical anesthesia for intravitreal Ozurdex injection.

• Ozurdex
• intravitreal injection
• nepafenac
• pain

• Bevacizumab
• Diabetic macular edema
• Diclofenac
• Intravitreal injection

To describe nepafenac use in the Netherlands and Denmark with reference to its approved indications. For context, we also describe the use of ketorolac and diclofenac.

We identified users in the PHARMO Database Network (the Netherlands, 2008–2013) and the Danish national health registers (Denmark, 1994–2014). We described prevalence of cataract surgery and duration of use in patients with cataract surgery with and without diabetes.

In the Netherlands, 9530 nepafenac users (mean age, 71 years; 60% women) contributed 12 691 therapy episodes, of which 21% had a recently recorded cataract surgery. Of 2266 episodes in adult non‐diabetic patients with cataract surgery, 60% had one bottle dispensed (treatment duration ≤21 days). Of 441 episodes in adult diabetic patients with cataract surgery, 90% had up to two bottles dispensed (≤60 days).

Denmark had 60 403 nepafenac users (mean age, 72 years; 58% women) and 73 648 episodes (41% had recorded cataract surgery). Of 26 649 nepafenac episodes in adult non‐diabetic patients with cataract surgery, 92% had one bottle dispensed. Of 3801 episodes in adult diabetic patients with cataract surgery, 99.8% had up to two bottles dispensed.

Use patterns of nepafenac, ketorolac and diclofenac were roughly similar in the Netherlands, but not in Denmark.

Less than half of therapy episodes were related to cataract surgery; around 90% of episodes with surgery were within the approved duration. Underrecording of ophthalmic conditions and procedures was a challenge in this study.

• cataract
• cataract surgery
• diclofenac
• ketorolac
• nepafenac
• off-label
• ophthalmic NSAIDs

• Anti-inflammatory Agents
• Bevacizumab
• Diabetic Macular Edema
• Diclofenac
• Intravitreal Injection

• Bevacizumab
• Diabetic Retinopathy
• Diabetic macular edema
• Diclofenac
• Intravitreal injection
• NSAIDs

• Amfenac
• PGE2
• aqueous humor
• ketorolac
• nepafenac
• vitreous humor

• clinical trials
• diabetic macular edema
• nonbiological pharmacotherapy
• nonsteroidal anti-inflammatory drugs
• steroids

• NSAIDs
• inflammation
• retinal disease
• vitreous penetration

• diabetic retinopathy clinical research network
• nepafenac
• non-central dme
• topical nsaid

• Administration, Topical
• Aged
• Anti-Inflammatory Agents, Non-Steroidal/administration & dosage
• Benzeneacetamides/administration & dosage
• Diabetes Mellitus, Type 1/complications
• Diabetes Mellitus, Type 2/complications
• Diabetic Retinopathy/drug therapy
• Diabetic Retinopathy/physiopathology
• Double-Blind Method
• Female
• Humans
• Macular Edema/drug therapy
• Macular Edema/physiopathology
• Male
• Middle Aged
• Ophthalmic Solutions
• Phenylacetates/administration & dosage
• Retina/pathology
• Tomography, Optical Coherence
• Visual Acuity/physiology

• UG1 EY014231 NEI NIH HHS
• U10 EY018817 NEI NIH HHS
• EY14231 NEI NIH HHS
• U10 EY014231 NEI NIH HHS
• U10 EY023207 NEI NIH HHS
• EY023207 NEI NIH HHS
• EY18817 NEI NIH HHS

• humans
• anti‐inflammatory agents, non‐steroidal
• anti‐inflammatory agents, non‐steroidal/therapeutic use
• diabetic retinopathy
• diabetic retinopathy/complications
• diabetic retinopathy/drug therapy
• macular edema
• macular edema/drug therapy
• macular edema/etiology

• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Diabetic Retinopathy/complications
• Diabetic Retinopathy/drug therapy
• Humans
• Macular Edema/drug therapy
• Macular Edema/etiology

Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively in ophthalmology for pain and photophobia after photorefractive surgery and to reduce miosis, inflammation, and cystoid macular edema following cataract surgery. In recent years, the US Food and Drug Administration has approved new topical NSAIDs and previously approved NSAIDs have been reformulated. These changes may allow for greater drug penetration into the retina and thereby offer additional therapeutic advantages. For example, therapeutic effects on diabetic retinopathy and age-related macular degeneration may now be achievable. We provide an updated review on the scientific rationale and clinical use of NSAIDs for retinal disease.

The purpose of this study was to evaluate nepafenac ophthalmic suspension 0.1% (Nevanac^®; Alcon Research Ltd) in the prevention of macular edema following cataract surgery in diabetic retinopathy patients.

This was a multicenter, randomized, double-masked, vehicle-controlled study of 263 adult diabetic patients with nonproliferative diabetic retinopathy requiring cataract surgery. Patients were randomized (1:1) to instill nepafenac or vehicle three times daily beginning 1 day prior to surgery through day 90. Efficacy included the percentage of patients who developed macular edema (≥30% increase in central subfield macular thickness from baseline) and the percentage of patients with decreases of more than five letters in best-corrected visual acuity from day 7 to 90.

A significantly lower percentage of patients in the nepafenac group developed macular edema relative to patients in the vehicle group (3.2% versus 16.7%; P < 0.001). A significantly lower percentage of patients in the nepafenac group had best-corrected visual acuity decreases of more than five letters relative to patients in the vehicle group on day 30 (P < 0.001), day 60 (P = 0.002), and day 90 (P = 0.006). The mean central subfield macular thickness and mean percent change from baseline in macular volume were also significantly lower in the nepafenac group versus the vehicle group at days 14 through 90 (P ≤ 0.005). No safety issues or trends were identified when dosing was increased to 90 days that negatively impacted the favorable benefit/risk profile of nepafenac.

Nepafenac demonstrated statistically significant and clinically relevant advantages compared with vehicle in preventing macular edema and maintaining visual acuity in diabetic patients following cataract surgery. These advantages were seen at multiple time points over the course of the 90-day therapy period. There was no clinically relevant increase in risk from 90 days dosing compared with 14 days. Therefore, with a similar safety profile and benefit in preventing macular edema and maintaining vision, the risk/benefit to the diabetic patient undergoing cataract surgery appears to be positive.

• cataract extraction
• diabetes
• macular edema
• nonsteroidal anti-inflammatory drug
• ocular surgery
• retinopathy
• topical

• celecoxib
• prodrugs
• transscleral
• melanin binding
• retinal delivery

• Animals
• Cattle
• Celecoxib
• Cell Line
• Cell Survival/drug effects
• Choroid/metabolism
• Chromatography, Liquid
• Humans
• In Vitro Techniques
• Male
• Melanins/metabolism
• Prodrugs/adverse effects
• Prodrugs/chemical synthesis
• Prodrugs/chemistry
• Prodrugs/pharmacokinetics
• Pyrazoles/adverse effects
• Pyrazoles/chemistry
• Pyrazoles/pharmacokinetics
• Rats
• Retina/metabolism
• Sclera/metabolism
• Sulfonamides/adverse effects
• Sulfonamides/chemistry
• Sulfonamides/pharmacokinetics
• Tandem Mass Spectrometry
• Vitreous Body/metabolism

• R01 EY017533 NEI NIH HHS
• R01 EY018940 NEI NIH HHS
• EY017533 NEI NIH HHS
• R01 EY017533-05 NEI NIH HHS
• EY018940 NEI NIH HHS
• R01 EY018940-02 NEI NIH HHS

To evaluate the effectiveness of prophylactic administration of nepafenac 0.1% in maintaining mydriasis and in preventing postoperative macular edema following cataract surgery.

This was a prospective, randomized, single-masked comparative study in 60 patients undergoing phacoemulsification cataract surgery. Patients were randomized to either the nepafenac or the control group. Nepafenac was administered 3 times daily 1 day before surgery and continued for 6 weeks. The control group received tobramycin-dexamethasone treatment only. Trans-operative mydriasis was measured before surgery, after nuclear emulsification, following cortex aspiration, and at the conclusion of surgery. Macular optical coherence tomography determined central foveal thickness (FT) and total macular volume (TMV) before surgery and at 2 and 6 weeks after surgery. All patients received tobramycin-dexamethasone for 2 weeks after surgery.

The difference in mean pupil size, at the end of surgery, between the control group (6.84 ± 0.93 mm) and the nepafenac group (7.91 ± 0.74 mm) was statistically significant (p < 0.001). There were no significant differences in FT values between the two groups at any time point; however, TMV at 2 and at 6 weeks was statistically significantly different (p < 0.001), with higher TMV in the control group.

Prophylactic use of nepafenac was effective in reducing macular edema after cataract surgery and in maintaining trans-operative mydriasis.

• cataract surgery
• macular edema
• mydriasis
• nepafenac
• prophylactic

To describe the use of nepafenac 0.1% for cystoid macular edema (CME).

This was a multicenter retrospective review of 22 CME cases (20 patients) treated with nepafenac 0.1% (six with concomitant prednisolone acetate 1%) from December 2005 to April 2008: three acute pseudophakic CME cases, 13 chronic/recalcitrant pseudophakic CME cases, and six cases of uveitic CME. Pre- and post-treatment retinal thickness and visual acuity were reported.

Following treatment for six weeks to six months, six eyes with uveitic CME showed a mean retinal thickness improvement of 227 ± 168.1 μm; mean best-corrected visual acuity (BCVA) improvement was 0.36 ± 0.20 logMAR. All three cases of acute pseudophakic CME improved after four to 10 weeks of nepafenac, with a mean improvement in retinal thickness of 134 ± 111.0 μm. BCVA improved in two patients (0.16 and 0.22 logMAR) but not in the third due to underlying retinal pigment epithelium changes. Thirteen eyes with chronic/recalcitrant pseudophakic CME demonstrated a mean improvement in retinal thickness of 178 ± 128.7 μm after nepafenac and mean BCVA improvement of 0.33 ± 0.19 logMAR.

The positive outcomes of these 22 eyes strongly suggest that nepafenac 0.1% is a promising drug for the treatment of CME. Additional study under randomized controlled conditions is warranted.

• NSAID
• cataract surgery
• macular edema
• nepafenac
• uveitis