Preoperative and intraoperative prognostic factors of epiretinal membranes using chromovitrectomy and internal limiting membrane peeling.

BACKGROUND AND OBJECTIVE: To evaluate the preoperative and intraoperative findings as prognostic indicators of functional and anatomic results of idiopathic epiretinal membrane (ERM) surgery. PATIENTS AND METHODS: Vitrectomies included ERM and internal limiting membrane (ILM) removal with vital dyes. Best corrected visual acuity (BCVA), optical coherence tomography (OCT), fluorescein angiography, and autofluorescence were performed at baseline and postoperatively. Intraoperative ILM status after ERM removal was also evaluated. RESULTS: Thirty-one eyes were monitored for a mean of 16.78 months. BCVA and central foveal thickness (CFT) improved significantly (P < .001) from baseline at 3 and 12 months. Preoperative hyperautofluorescence was associated with greater CFT reduction (P < .005). ILM status after ERM peeling did not influence visual recovery but was associated with anatomical results as measured by OCT. CONCLUSION: Preoperative poor initial BCVA and RPE defects by FAF may not be bad prognostic factors. Preoperative hyperautofluorescence was associated with greater CFT reduction. Intraoperative classification of ILM status after ERM and ILM staining/peeling was reported and may be useful for future studies, though it was not associated neither with preoperative nor postoperative BCVA.

Lutein and zeaxanthin toxicity with and without brilliant blue in rabbits.

PURPOSE: To evaluate the safety profile of solutions containing lutein and zeaxanthin alone or associated with brilliant blue (BB). METHODS: Twenty-eight New Zealand rabbits were used to evaluate 4 concentrations of the various dye solutions: 0.5% lutein/zeaxanthin; 0.5% lutein/zeaxanthin associated with 0.0125% BB; 0.3% lutein/zeaxanthin associated with 0.025% BB; and 0.25% lutein/zeaxanthin associated with 0.05% BB. The pHs of the dye solutions ranged from 6.5 to 7.2 and the osmolarities from 280 to 320 mOsm/mL. Each rabbit had 0.1 mL of one of the dyeing solutions injected into the vitreous cavity of the right eye, while balanced salt solution (BSS) was injected into the left eye as the control. Scotopic electroretinography responses were recorded in all eyes at different time points. The animals were sacrificed at 1 and 7 days after injection; the eyes were analyzed by light and transmission electron microscopy. RESULTS: No significant (P>0.05) differences were seen in the a- and b-wave amplitudes among groups at any given point in time. Light and electron microscopy findings showed no significant abnormalities either, and were similar to the histological findings after intravitreal BSS injection. CONCLUSIONS: Lutein and zeaxanthin alone or in association with BB showed a good safety profile in this experimental model.

Soluble lutein in combination with brilliant blue as a new dye for chromovitrectomy.

UNLABELLED: A new dye for vitreoretinal surgery comprised of soluble lutein/zeaxanthin 1 % and brilliant blue 0.025 % is advantageous compared with other dyes currently used for chromovitrectomy, and showed no signs of toxicity at 1 month of follow-up. PURPOSE: To evaluate the feasibility and safety of a dye [soluble lutein/zeaxanthin (LZ) 1 % and brilliant blue (BB) 0.025 %] for improving removal of vitreous, epiretinal membranes (ERM), and internal limiting membranes (ILM) in humans. METHODS: We prospectively evaluated 18 eyes treated surgically for a macular hole or ERM. Eighteen surgeons performed chromovitrectomy using the dye, and completed a questionnaire to evaluate the efficacy and safety of the dye. . Examinations included best-corrected visual acuity and intraocular pressure measurements and optical coherence tomography, fluorescein angiography, and autofluorescence performed at baseline and days 1, 7, and 30 postoperatively. RESULTS: The green dye was deposited on the posterior pole; vigorous dye flushing into the vitreous cavity was unnecessary. All surgeons reported that the ILM stained greenish-blue; 94.4 % reported ILM peeling adequate; the ERM stained poorly. No evidence of toxicity was observed. CONCLUSION: The new dye deposited on the posterior pole due to its higher density. The ability to stain the ILM was similar to BB. The new dye has ability to stain the vitreous, hyaloid, and especially the ILM satisfactorily. The new dye may be useful during chromovitrectomy.

Lutein: a new dye for chromovitrectomy.

PURPOSE: To evaluate the feasibility, advantages, and safety of a novel lutein-based dye for improving identification and removal of the vitreous, internal limiting membrane, and epiretinal membrane during chromovitrectomy in humans. METHODS: We prospectively evaluated 12 eyes that underwent pars plana vitrectomy using the dye in patients with macular hole, epiretinal membrane, or proliferative diabetic retinopathy/tractional diabetic macular edema. One surgeon performed standard chromovitrectomy and completed a postoperative questionnaire to compare the staining with that of the available dyes. The peeled membranes were evaluated histologically. Follow-up examinations were performed on postoperative Days 1, 7, 30, 90 and 180; best-corrected visual acuity, optical coherence tomography, fluorescein angiography, autofluorescence, and visual fields were performed. RESULTS: The green dye was deposited on the posterior pole because of its higher density than balanced saline solution; vigorous dye flushing into the vitreous cavity was unnecessary. The dye stained the posterior hyaloid/vitreous base by deposition onto the vitreous; brilliant blue stained the internal limiting membrane. The epiretinal membrane was poorly stained. The best-corrected visual acuity improved in all eyes without clinical toxicity or toxicity on images/visual fields. Histology showed effective removal of the internal limiting membrane and epiretinal membrane in all eyes. CONCLUSION: The new dye improved intraoperative identification of the internal limiting membrane and the posterior hyaloid/vitreous base during chromovitrectomy.

In vivo, in vitro toxicity and in vitro angiogenic inhibition of sunitinib malate.

PURPOSE: To evaluate the in vivo and in vitro toxicity of sunitinib malate, a multikinase inhibitor molecule. DESIGN: Experimental, Prospective, Controlled. METHODS: Human retinal pigment epithelial (ARPE-19) and human umbilical vein endothelialcells (HUVECS) were used in a culture toxicity test and exposed to different concentrations of sunitinib malate for 18 hours. The HUVECs also were cultured to evaluate the angiogenesis inhibitory effect of sunitinib malate. Fundus photography and angiographic, electrophysiologic, and histopathologic evaluations with light and electron microscopy were performed in two groups of five rabbits each that received different intravitreal concentrations of the drug. Each rabbit received 0.1 ml of sunitinib malate in the right eye (one group with 12.5 mg/ml, the other group with 25 mg/ml); all animals received 0.1 ml of physiologic saline solution in the left eye. After sacrifice, the eyes were enucleated and fixed with modified Karnovsky solution. RESULTS: No toxicity related to sunitinib malate was observed using an in vitro model with the 12.5 and 25 mg/ml solutions in HUVEC and ARPE cell cultures. No toxicity was observed in the in vivo model with 12.5 mg/ml, but light microscopy showed that the 25 mg/ml solution damaged the photoreceptors layer. No functional changes in the electroretinogram were observed in any group. CONCLUSIONS: Sunitinib malate 12.5 mg/ml caused no toxicity in in vivo and in vitro models, but the 25 mg/ml concentration caused retinal changes suggesting toxicity in the in vivo model. Further research with the drug is needed in models of ocular neovascularization.

Toxicological considerations for intravitreal drugs.

INTRODUCTION: Intravitreal injections are a very common procedure and are the most effective route of drug delivery to the retina. There are currently several drugs available and even more are in development; therefore, safety is a very important concern. AREAS COVERED: The toxicological considerations of the most common drugs used for intravitreal pharmacotherapy such as anti-VEGFs, corticosteroids and antibiotics. Emerging agents such as anti-TNFs, VEGF-trap and kinase inhibitors are also discussed. An assessment of the efficacy and safety issues of the most relevant drugs including bevacizumab, ranibizumab and triamcinolone is presented. EXPERT OPINION: The toxicology and safety profiles are available for several drugs that are either in use or will be available for intravitreal injections. Retinal pharmacotherapy is very effective for different retinal diseases; however safety is a very important issue when intravitreal injections are applied and the possibility of retinal toxicity should always be kept in mind. Bevacizumab and ranibizumab are effective for the therapy of wet-age-related macular degeneration and macular edema, while triamcinolone remains an alternative agent to treat secondary macular edema. It is important, as some of these drugs will be used for extended periods of time, that their long-term toxicological effects are better understood.

Retinal and ocular toxicity in ocular application of drugs and chemicals--part II: retinal toxicity of current and new drugs.

AIMS: Retinal pharmacotherapy has gained great importance for the treatment of various retinal diseases. An increasing number of drugs have been constantly released into the market, especially for wet age-related macular disease and diabetic macular edema. In this review, the issues concerning the toxicity of current and new classes of drugs are discussed. METHODS: An extensive search of the literature was performed to review various aspects of drug toxicity in retinal pharmacotherapy. The different major classes of drugs, such as corticosteroids, antibiotics, antimetabolites, antineoplastic agents, monoclonal antibodies (mAbs), nonsteroidal anti-inflammatory drugs, enzymes, fibrinolytics, miscellaneous anti-inflammatory and antiangiogenic agents, as well as toxicity unrelated to the drug were identified and discussed. RESULTS: Corticosteroids like fluocinolone, dexamethasone or triamcinolone at low dose cause little damage to the retina, but at high doses signs of toxicity have been well documented. Complications like cataract and glaucoma are quite common with corticosteroids. Aminoglycosides showed differences in the type and doses associated with toxic reactions, thereby the following order of toxicity can be described (from most toxic to least toxic): gentamicin > netilmicin = tobramycin > amikacin = kanamycin. Vancomycin at the usual dose of 1 mg is not toxic to the retina, while further studies are necessary in order to clarify the safety of new-generation quinolones. 5-Fluorouracil has been shown to be nontoxic to the retina after an injection of 2.5 mg in animals. mAbs like ranibizumab and bevacizumab were demonstrated to be safe to the retina in cell culture, animals and humans at high doses. The exact biocompatibility of nonsteroidal anti-inflammatory agents like diclofenac needs further evaluation. Preservatives like benzyl alcohol and changes in pH or osmolarity exert an influence on the toxic effects of intravitreally applied drugs. CONCLUSIONS: A great number of drugs are now used mainly intravitreally without relevant retinal toxicity.

Retinal and ocular toxicity in ocular application of drugs and chemicals--part I: animal models and toxicity assays.

AIMS: Experimental retinal research has gained great importance due to the ophthalmic pharmacotherapy era. An increasing number of drugs are constantly released into the market for the treatment of retinal diseases. In this review, animal species, animal models and toxicity assays in retinal research are discussed. METHODS: An extensive search of the literature was performed to review various aspects of the methods of investigation of drug toxicity. The different types of animal species, as well as single animal models available for the evaluation of safety and efficacy of retinal pharmacotherapy, were identified. In addition, a large variety of reported laboratory techniques were critically examined. RESULTS: In vitro studies are the first-line experiments for the development of a new drug for retinal diseases, using retinal pigment epithelial cells and other cell lines. The next step involves in vivo animal studies where nonhuman primates are considered the gold standard. However, cost and legal issues make their use difficult. Mice and rats provide genetically controlled models for investigations. Pigs, dogs and cats represent good large-size animal models, while rabbits are one of the most used species for retinal toxicity evaluations. Various laboratory methods were identified, including light microscopy, electron microscopy, electroretinography and new emerging methods, such as optical coherence tomography and scanning laser ophthalmoscopy for experimental purposes. CONCLUSIONS: A great number of animal species and models are available that simulate retinal diseases and provide experimental data for further human use. Work with animal models should include properly designed toxicity assays to obtain reliable results for safety and efficacy.

Corantes vitais em cromovitrectomia / Vital dyes in chromovitrectomy

O objetivo do artigo é apresentar os dados atuais da aplicação de corantes vitais durante cirurgia vitreorretiniana, "cromovitrectomia", bem como uma revisão da literatura atual sobre o assunto no tocante às técnicas de aplicação, indicações e complicações em cromovitrectomia. Um grande número de publicações tem abordado o perfil tóxico da indocianina verde na cromovitrectomia. Dados experimentais mostram uma toxicidade dose-dependente da mesma em várias populações de células retinianas. Novas gerações de corantes incluem: azul tripan, azul patente, acetato de triancinolona, infracianina verde, fluoresceína sódica, azul de bromofenol, acetato de fluorometolona e azul brilhante. Novos instrumentos podem permitir um corar seletivo de estruturas durante a vitrectomia. Este artigo mostra que o campo da cromovitrectomia está em plena expansão de pesquisas. Os corantes de primeira linha são a indocianina verde, infracianina verde e o azul brilhante. Azul patente, azul de bromofenol e azul tripan surgem como novos adjuvantes para melhor observação da membrana epirretiniana. Demais corantes que surgiram merecem maior investigação.

The aim of this article is to present the current data with regard to the application of vital dyes during vitreoretinal surgery, "chromovitrectomy", as well as to overview the current literature regarding the properties of dyes, techniques of application, indications and complications in chromovitrectomy. A large body of published research has recently addressed the toxicity profile of indocyanine green for chromovitrectomy. Experimental data demonstrate dose-dependent toxicity of indocyanine green to various retinal cells. Newer generation vital dyes for chromovitrectomy include trypan blue, patent blue, triamcinolone acetonide, infracyanine green, sodium fluorescein, bromophenol blue, fluorometholone acetate and brilliant blue. Novel instruments may enable a selective painting of preretinal tissues during chromovitrectomy. This review suggests that the field of chromovitrectomy represents an expanding area of research. The first line agents for internal limiting membrane staining in chromovitrectomy are indocyanine green, infracyanine green, and brilliant blue. Patent blue, bromophenol blue and trypan blue arose as outstanding biostains for visualization of epiretinal membranes. Novel dyes available for chromovitrectomy deserve further investigation.

The use of vital dyes in ocular surgery.

Vital dyes have advanced diagnosis and surgical technique in various specialties, including oncology, gastroenterology, and ophthalmology. In ocular surgery vital dyes are widely used in cataract and vitreoretinal surgery. Worldwide, intra-operative use of trypan blue during cataract surgery has enhanced visualization of the anterior capsule during capsulorrhexis, and patent blue has been recently licensed in Europe for cataract surgery. For chromovitrectomy, the vital dyes indocyanine green, infracyanine green, and brilliant blue stain the internal limiting membrane, and trypan blue and triamcinolone acetonide help visualize epiretinal membranes and vitreous, respectively. Intra-operative vital dyes are finding uses in corneal, glaucoma, orbit, strabismus, and conjunctival surgery. We provide a summary of current knowledge of the use of vital dyes in ocular surgery. We review the properties of dyes, techniques of application, indications, and complications in ocular surgery. Vital dyes represent an expanding area of research, and novel dyes deserve further investigation.

Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve fiber layer and optic nerve appearance.

OBJECTIVE: To determine if panretinal photocoagulation (PRP) alters retinal nerve fiber layer (RNFL) thickness and optic nerve appearance. METHODS: Patients with diabetes who did and did not undergo PRP and nondiabetic control subjects were enrolled in a prospective study. Participants underwent optical coherence tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve photographs were graded in a masked fashion. RESULTS: Ninety-four eyes of 48 healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and 37 eyes of 24 subjects with diabetes who underwent PRP were included in this study. Eyes that had been treated with PRP had thinner peripapillary RNFL compared with the other groups; this was statistically significantly different in the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not increase with severity of disease classification, but the proportion of optic nerves graded as suspicious for glaucoma or as having nonglaucomatous optic neuropathy did (P = .008). These grading categories were associated with thinner RNFL measurements. CONCLUSIONS: Diabetic eyes that have been treated with PRP have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP are more likely to be graded as abnormal, but their appearance is not necessarily glaucomatous and may be related to thinning of the RNFL.

[Sight-threatening orbital emphysema after nose blowing: case report]. / Enfisema orbitário compressivo após asseio nasal: relato de caso.

Orbital emphysema is the abnormal presence of air in the orbit. Occurrence in the absence of orbital fracture is rare. We report a case of a 40-year-old female presenting unilateral orbital emphysema after vigorous nose blowing. She developed sudden visual loss as a result of elevated intraocular pressure and urgent treatment was required. She underwent an orbital decompression, performed using a 24-gauge needle puncture adjacent to the supraorbital notch. After treatment, she reported considerable decrease of symptoms.

Enfisema orbitário compressivo após asseio nasal: relato de caso / Sight-threatening orbital emphysema after nose blowing: case report

O enfisema orbitário é caracterizado pela presença anormal de ar na órbita. Sua ocorrência espontânea não é frequente e a maioria dos casos está associada à fratura de órbita. Relatamos o caso de uma paciente do sexo feminino de 40 anos com quadro de enfisema orbitário unilateral, secundário a asseio vigoroso do nariz. A paciente evoluiu com redução aguda da acuidade visual em decorrência de elevação da pressão intraocular, sendo indicado tratamento de urgência. Foi realizada punção orbitária com agulha 24-gauge próximo à região da incisura supraorbital, com melhora imediata do quadro clínico e recuperação da acuidade visual.

Orbital emphysema is the abnormal presence of air in the orbit. Occurrence in the absence of orbital fracture is rare. We report a case of a 40-year-old female presenting unilateral orbital emphysema after vigorous nose blowing. She developed sudden visual loss as a result of elevated intraocular pressure and urgent treatment was required. She underwent an orbital decompression, performed using a 24-gauge needle puncture adjacent to the supraorbital notch. After treatment, she reported considerable decrease of symptoms.

Preclinical investigation of the retinal biocompatibility of six novel vital dyes for chromovitrectomy.

PURPOSE: To investigate the retinal biocompatibility of six novel vital dyes for chromovitrectomy. METHODS: An amount of 0.05 mL of 0.5% and 0.05% light green (LG), fast green (FG), Evans blue (EB), brilliant blue (BriB), bromophenol blue (BroB), or indigo carmine (IC) was injected intravitreally in the right eye, whereas in the left eye balanced salt solution was applied for control in rabbits' eyes. Clinical examination, fluorescein angiography, histology with light microscopy, and transmission electron microscopy were performed after 1 and 7 days. Retinal cell layers were evaluated for morphologic alterations and number of cells. The electroretinographic changes were assessed at baseline, 24 hours and 7 days. RESULTS: Fluorescein angiography disclosed hypofluorescent spots only in the 0.5% EB group. Light microscopy and transmission electron microscopy disclosed slight focal morphologic changes in eyes exposed to 0.05% IC, FG, BriB, similar to the control at 1 and 7 days. In the lower dose groups, EB, LG, and BroB caused substantial retinal alterations by light microscopy. At the higher dose, BroB and EB produced diffuse cellular edema and vacuolization within the ganglion cells, bipolar cells, and photoreceptors. FG and IC at 0.5% caused slight retinal alterations similar to balanced salt solution injection. LG at 0.5% caused diffuse vacuolization of bipolar cells after 1 and 7 days. Injection of 0.5% EB caused a significant decrease in neuroretinal cell counts in comparison to control eyes in the 7-day examination (P < 0.05). Electroretinography revealed intermittent prolonged latency and decreased amplitude in eyes injected with 0.5% EB, LG, BriB, and BroB, while at the lower dose, only LG and EB induced few functional changes. CONCLUSION: The progressive order of retinal biocompatibility, from safest to most toxic, was IC, FG, BriB, BroB, LG, EB.

[Vital dyes in chromovitrectomy]. / Corantes vitais em cromovitrectomia.

The aim of this article is to present the current data with regard to the application of vital dyes during vitreoretinal surgery, 'chromovitrectomy', as well as to overview the current literature regarding the properties of dyes, techniques of application, indications and complications in chromovitrectomy. A large body of published research has recently addressed the toxicity profile of indocyanine green for chromovitrectomy. Experimental data demonstrate dose-dependent toxicity of indocyanine green to various retinal cells. Newer generation vital dyes for chromovitrectomy include trypan blue, patent blue, triamcinolone acetonide, infracyanine green, sodium fluorescein, bromophenol blue, fluorometholone acetate and brilliant blue. Novel instruments may enable a selective painting of preretinal tissues during chromovitrectomy. This review suggests that the field of chromovitrectomy represents an expanding area of research. The first line agents for internal limiting membrane staining in chromovitrectomy are indocyanine green, infracyanine green, and brilliant blue. Patent blue, bromophenol blue and trypan blue arose as outstanding biostains for visualization of epiretinal membranes. Novel dyes available for chromovitrectomy deserve further investigation.

Vital dyes and light sources for chromovitrectomy: comparative assessment of osmolarity, pH, and spectrophotometry.

PURPOSE: To investigate the in vitro pH, osmolarity, spectral, and photostability properties of nine vital dyes for vitreoretinal surgery. METHODS: Nine dyes-indocyanine green (ICG), trypan blue (TB), brilliant blue (BriB), bromophenol blue (BroB), Congo red (CR), light green (LG), fast green (FG), indigo carmine (IC) and Evans blue (EB)-diluted in three solvents (saline solution, glucose 5%, and water) were tested for osmolarity and pH. Spectrophotometry was used to determine absorbance properties of 27 solutions. Irradiance emission spectra of seven endoillumination light sources and fiber-optics were compared with dye absorbance curves. RESULTS: Dye osmolarity in saline solution and glucose 5% varied widely (257-385 mOsm) and was lower (0-54 mOsm) when dyes were dissolved in water. Dyes diluted in three solvents showed pH values varying from 2.6 to 9.85. ICG, LG, TB, BroB, CR, and IC demonstrated different absorbances, depending on the solvent. BriB and FG showed similar absorbance curves with different solvents. Spectrophometric analysis showed that all dyes except ICG had remarkable spectral overlap with the light sources. Among endoillumination fiber-optics, overlap was greatest with dual-output illumination with an integrated laser pathway and least with a mercury vapor lamp. CONCLUSIONS: Vital dyes showed variable osmolarity and pH, which also depended on the solvent used. Interaction of light from endoillumination source and vital dye may increase or decrease the risk for toxicity, making appropriate selection of both a desirable way to minimize the risk for phototoxic effects.

Historical aspects and evolution of the application of vital dyes in vitreoretinal surgery and chromovitrectomy.

Lobeck and coworkers performed the first intravitreal application of vital dyes to visualize preretinal structures in 1932. Since then numerous investigators in the 20th century examined the use of biological stains through the endovenous, subretinal and intravitreal delivery route in order to identify vitreoretinal tissues and breaks. However, in the year 2000, a new surgical approach, recently coined chromovitrectomy, has arisen, which consists in the intraoperative application of vital dyes during vitrectomy. Initially fluorescein, and more recently indocyanine green, trypan blue, bromophenol blue, triamcinolone acetonide and patent blue have been used for the staining of preretinal membranes and tissues. Currently, many vital stains are under evaluation in animals for future clinical application during chromovitrectomy such as indigo carmine or light green. In this paper, several historical considerations in regard to the application of vital dyes in chromovitrectomy are discussed.

Current concepts of trypan blue in chromovitrectomy.

Trypan blue (TB) is a blue vital dye with fine color properties to stain the anterior lens capsule and thereby may facilitate capsulorrhexis during cataract surgery. In addition, the blue stain may assist in the visualization of various preretinal membranes and tissues during vitreoretinal surgery in a procedure also called chromovitrectomy. TB has demonstrated great binding affinity for the glial epiretinal membranes, although it remains yet to be determined in which circumstances the dye may color the vitreous and internal limiting membrane. Most studies suggest that 0.06% TB does not pose harm to the retina, but at higher concentrations further investigation is necessary. In this paper, various aspects of the application of TB for chromovitrectomy are discussed including laboratory investigations, surgical technique and clinical outcomes.

Emerging pharmacotherapies for diabetic macular edema.

Diabetic macular edema (DME) is the most frequent cause of severe vision impairment in patients with non-proliferative diabetic retinopathy. Even though patients should achieve optimal glycemic control, normalization of blood pressure and serum lipids, as well as improvement of cardiac and renal status, these measures alone will not prevent every patient from developing visual loss caused by DME. The goal of local treatment for DME is vision improvement, usually achieved after reducing leakage on fluorescein angiography (FA) and retinal thickness on optical coherence tomography (OCT). Laser photocoagulation is still the standard treatment for clinically significant DME. However, laser photocoagulation rarely provides major visual improvement, especially in patients with diffuse DME. Thus, a therapeutic intervention that restores visual acuity impaired by DME more often remains a significant unmet medical need. This review aims to present the most important emerging drug technologies for therapy of DME at present, including corticosteroids, vascular endothelial growth factor inhibitors, protein kinase C inhibitors, small interfering RNA, hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors and non-hormonal anti-inflammatory agents. Recent progress in this field suggests that local management of DME may change rapidly in the near future. Novel emerging drugs should enable better anatomical and functional outcomes for therapy of this sight-threatening disease.