Bruno Furlani

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.

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.

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.

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.

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.

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.

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.

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.

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.