A new dye for vitreoretinal surgery comprised of soluble lutein/zeaxanthin 1 % and brilliant blue... more 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. 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. 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. 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. 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.
Most of current concepts for a visual prosthesis are based on neuronal electrical stimulation at ... more Most of current concepts for a visual prosthesis are based on neuronal electrical stimulation at different locations along the visual pathways within the central nervous system. The different designs of visual prostheses are named according to their locations (i.e., cortical, optic nerve, subretinal, and epiretinal). Visual loss caused by outer retinal degeneration in diseases such as retinitis pigmentosa or age-related macular degeneration can be reversed by electrical stimulation of the retina or the optic nerve (retinal or optic nerve prostheses, respectively). On the other hand, visual loss caused by inner or whole thickness retinal diseases, eye loss, optic nerve diseases (tumors, ischemia, inflammatory processes etc.), or diseases of the central nervous system (not including diseases of the primary and secondary visual cortices) can be reversed by a cortical visual prosthesis. The intent of this article is to provide an overview of current and future concepts of retinal and optic nerve prostheses. This article will begin with general considerations that are related to all or most of visual prostheses and then concentrate on the retinal and optic nerve designs. The authors believe that the field has grown beyond the scope of a single article so cortical prostheses will be described only because of their direct effect on the concept and technical development of the other prostheses, and this will be done in a more general and historic perspective.. ( Surv Ophthalmol 47 :335-356, 2002.
Raman spectroscopy iris endophthalmitis uveitis differential diagnosis principal components analy... more Raman spectroscopy iris endophthalmitis uveitis differential diagnosis principal components analysis Mahalanobis distance discriminant analysis a b s t r a c t
To evaluate histopathological retinal and renal response after one single dose of intravitreous i... more To evaluate histopathological retinal and renal response after one single dose of intravitreous injection of antiangiogenic drugs ranibizumab and bevacizumab in rats. Experimental study in 60d of life adults Wistar rats. Ten animals were included. Group 1 included 5 animals that were injected with 1 µL ranibizumab 1.25 mg in the right eye and with 1 µL of balanced salt solution (BSS) in the left eye, as control; Group 2 included 5 animals that were injected with 1 µL of bevacizumab in the right eye and with 1 µL of BSS in the fellow eye. All injections were performed with Hamilton syringes. After 15d of the interventions, all animals were sacrificed in CO2 chamber. Both eyes were enucleated and one kidney was removed, fixed and embedded in paraffin for histopathological analysis by optic microscopy. For statistical purposes the initial expected abnormal histopathological responses were defined as 0%. Atypical histopathological retinal response was detected in 2 eyes injected with ra...
IEEE Transactions on Neural Systems and Rehabilitation Engineering, 2006
Experiments were conducted to assess the effect of stimulating electrode parameters (size, positi... more Experiments were conducted to assess the effect of stimulating electrode parameters (size, position, and waveform shape) on electrically elicited ganglion cell action potentials from isolated rabbit retina. Thirty-eight isolated rabbit retinas were stimulated with bipolar stimulating electrodes (either 125 or 25 mum in diameter) positioned on either the ganglion or the photoreceptor side. Recording electrodes were placed between the optic
Data comparing systemic exposure and systemic vascular endothelial growth factor (VEGF) suppressi... more Data comparing systemic exposure and systemic vascular endothelial growth factor (VEGF) suppression of ranibizumab, bevacizumab and aflibercept following intravitreal injection are lacking. Fifty-six patients with wet age-related macular degeneration received intravitreal ranibizumab (0.5 mg), bevacizumab (1.25 mg), or aflibercept (2.0 mg). Serum pharmacokinetics and plasma free VEGF were evaluated after the first and third injections. Following the first dose, systemic exposure to aflibercept was 5-, 37-, and 9-fold higher than ranibizumab, whereas, bevacizumab was 9-, 310-, and 35-fold higher than ranibizumab, based on geometric mean ratio of peak and trough concentrations and area under the curve, respectively. The third dose showed accumulation of bevacizumab and aflibercept but not ranibizumab. Aflibercept substantially suppressed plasma free VEGF, with mean levels below lower limit of quantitation (10 pg/mL) as early as 3 h postdose until ≥7 days postdose. Mean free (unbound) ...
Retina-the Journal of Retinal and Vitreous Diseases, 2002
Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for RETINA. Enter you... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for RETINA. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your ...
To report the clinical, electrophysiologic, and histologic findings of different concentrations o... more To report the clinical, electrophysiologic, and histologic findings of different concentrations of indocyanine green (ICG) injected into the vitreous cavity of rabbit eyes. Forty-two rabbits underwent intravitreal injection of 0.1 mL of ICG in three different concentrations: 0.5 mg/mL (250 mOsm), 5 mg/mL (270 mOsm), and 25 mg/mL (170 mOsm). Fellow eyes were injected with 0.1 mL of balanced salt solution. Biomicroscopy, ophthalmoscopy, electroretinography, fluorescein angiography, and histologic evaluation were performed. Eyes injected with 0.5 mg/mL of ICG showed b-wave latency delay on the first day after injection. Eyes injected with 5 mg/mL of ICG showed b-wave latency delay and decreased b-wave amplitude on the first and seventh days after injection; delayed a-wave latency on the first day after injection was also observed. Eyes injected with 25 mg/mL of ICG showed b- and a-wave amplitude and latency abnormalities during the entire follow-up. Direct correlation of increasing ret...
To evaluate the effects of indocyanine green (ICG) injection on the retinal surface and into the ... more To evaluate the effects of indocyanine green (ICG) injection on the retinal surface and into the subretinal space of rabbit eyes. Twenty-two Dutch-belted rabbits underwent two-port vitrectomy followed by injection of ICG (5 mg/mL) on the retinal surface and into the subretinal space. Balanced salt solution (BSS) was also injected subretinally. The locations where ICG was delivered (both epiretinal and subretinal) were exposed to light from an endoilluminator for 7 minutes. The animals were examined at 1, 7, and 14 days after surgery. The eyes were studied by fluorescein angiography as well as light and electron microscopy. No damage was observed after epiretinal ICG injection, but subretinal ICG injection resulted in damage to the outer nuclear layer, photoreceptor inner and outer segments, and retinal pigment epithelium. This damage was more severe with longer follow-up. Control experiments without ICG, in which balanced salt solution was injected into the subretinal space or light...
... MAIA, MAURICIO MD; HALLER, JULIA A. MD; PIERAMICI, DANTE J. MD; MARGALIT, EYAL MD, PhD; DE JU... more ... MAIA, MAURICIO MD; HALLER, JULIA A. MD; PIERAMICI, DANTE J. MD; MARGALIT, EYAL MD, PhD; DE JUAN, EUGENE JR. ... Baltimore, Maryland, USA; the Doheny Retina Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA ...
Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leadin... more Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leading cause in the population between 20 and 60 years old. Among patients with DR, diabetic macular edema (DME) is the most frequent cause of vision impairment and represents a significant public health issue. Macular photocoagulation has been the standard treatment for this condition reducing the risk of moderate visual loss by approximately 50%. The role of vascular endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated in recent studies. This review addresses and summarizes data from the clinical trials that investigated anti-VEGF for the management of DME and evaluates their impact on clinical practice. The literature searches were conducted between August and October 2013 in PubMed and Cochrane Library with no date restrictions and went through the most relevant studies on pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. The eff...
To investigate the histologic and clinical effects of subretinal injection of patent blue (PB) an... more To investigate the histologic and clinical effects of subretinal injection of patent blue (PB) and trypan blue (TB) in rabbits. Dutch-belted rabbits (n=8) were vitrectomized followed by subretinal injection of 2.4 mg/ml PB (285 mOsm) and 1.5 mg/ml TB (312 mOsm); balanced salt solution (BSS) (300 mOsm) served as the control. Animals were examined 6, 12, and 24 hr and 14 days after the procedure by fluorescein angiography (FA) and indirect ophthalmoscopy; for retinal toxicity, histologic evaluation studies were performed by light and transmission electron microscopy. FA examination demonstrated window defects suggestive of retinal pigment epithelium (RPE) atrophy in positions of subretinal TB injection, but this was not observed after subretinal injection of PB or BSS. Histologic evaluation disclosed only minimal abnormalities on the photoreceptor outer segment (POS) after subretinal injection of BSS during all follow-up. Subretinal injection of PB caused POS and photoreceptor inner s...
To investigate the retinal biocompatibility of Brilliant Blue G with deuterated water (BBG-D2O) a... more To investigate the retinal biocompatibility of Brilliant Blue G with deuterated water (BBG-D2O) as a vital dye for chromovitrectomy. In this animal study, 0.05 mL of 0.25 g/L Brilliant Blue G (BBG) associated with 0.13 mL/mL of deuterium oxide (D2O) was injected intravitreally in the right eye and the same amount of balanced salt solution (BSS) was injected similarly in the left eye of rabbits. Clinical examination and histology with light microscopy were performed after seven days. Retinal cell layers were evaluated for morphologic alterations. Electroretinographic (ERG) changes were also assessed at baseline and 7 days after the injections. A total of 6 rabbits were included in the study. The gross histopathologic appearance of the retina, choroid, sclera and optic nerve was within normal limits without any sign of severe retinal necrosis or cystic degeneration. Light microscopy showed that BBG-D2O caused no substantial alterations in retinal layers as compared to control eyes. Th...
Investigative ophthalmology & visual science, Jan 19, 2015
Purpose: To investigate and compare the mechanism by which lutein-based and synthetic intraocular... more Purpose: To investigate and compare the mechanism by which lutein-based and synthetic intraocular dyes interact with their target membranes during ophthalmic surgeries. Methods: Surrogate membrane models were used in order to simulate the different intraocular membranes: internal limiting membrane (ILM), vitreous, anterior capsule (AC) and epiretinal membrane (ERM). Different lutein-based dyes, such as Phacodyne, Retidyne, Retidyne Plus and Vitreodyne were tested, as well as Trypan Blue (TB), Indocyanine Green (ICG), Brilliant Blue (BB) and Triamcinolone Acetonide (TA). The interactions between the film components occurring at the air-water interface were investigated with surface pressure-area isotherms and polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS). Results: With the exception of TA and ICG, none of the tested dyes revealed toxicity to the analyzed membranes. The interaction of TA with the vitreous model affected deeply the biointerface structur...
To describe the systemic pharmacokinetics of ranibizumab after intravitreal administration in pat... more To describe the systemic pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion (RVO) or diabetic macular edema (DME). A population approach of nonlinear mixed-effect pharmacokinetics modeling based on serum concentrations of ranibizumab measured at various times after intravitreal administration. Patients with RVO (n = 441) and DME (n = 435) from 4 large, randomized, phase 3 clinical trials of monthly ranibizumab intravitreal administration. A 1-compartment pharmacokinetics model with first-order absorption and elimination rate constants previously developed in patients with age-related macular degeneration (AMD) was fitted separately to RVO and DME data. Population pharmacokinetic parameters and interindividual variability were estimated for each model. Baseline covariates were evaluated for potential effects on systemic pharmacokinetics. Model performance was validated using general diagnostic plots and a visual predictive check. Ranibizumab disposition was determined in RVO and DME patients and compared with that previously seen in AMD patients. The AMD pharmacokinetics model correctly predicted the measured serum ranibizumab concentration data for RVO and DME patients. Most observed data points were within the simulated 90% confidence interval, indicating that systemic ranibizumab concentrations were comparable among AMD, RVO, and DME patients. No disease-related covariates were identified by the population pharmacokinetics analysis. The systemic pharmacokinetics of ranibizumab were similar among patients with AMD, RVO, or DME. Disease-related differences and patient demographics, measured in this study, did not lead to variability in ocular elimination or in systemic exposure of ranibizumab after intravitreal administration. In all disease processes tested, ranibizumab exits the eye slowly and then is eliminated rapidly from the circulation, thus minimizing systemic exposure.
We report a case of a 19-year-old woman presenting bilateral neurosensorial hearing loss, mental ... more We report a case of a 19-year-old woman presenting bilateral neurosensorial hearing loss, mental abnormalities, and loss of visual field in the left eye. Visual acuity was 20/20 in OD and 20/25 in OS. Patient was examined systemically. Audiometry showed sensorineural hearing loss in both ears. The magnetic resonance imaging (MRI) of brain revealed multiple small lesions in the white matter in both cerebral hemispheres and at the corpus callosum. Fundoscopy showed bilateral normal optic disc and sheathing of the arterioles in the middle periphery of OD. Retinal edema and cotton-wool spots were observed. Fluorescein angiography showed bilateral peripheral occlusive arterial vasculopathy. The patient was diagnosed with Susac syndrome and treated with quetiapine fumarate, flunitrazepam, and prednisone, which resulted in stabile outcome. This case shows that a high index of suspicion leading to early recognition and treatment is important to avoid irreversible damage.
A new dye for vitreoretinal surgery comprised of soluble lutein/zeaxanthin 1 % and brilliant blue... more 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. 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. 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. 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. 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.
Most of current concepts for a visual prosthesis are based on neuronal electrical stimulation at ... more Most of current concepts for a visual prosthesis are based on neuronal electrical stimulation at different locations along the visual pathways within the central nervous system. The different designs of visual prostheses are named according to their locations (i.e., cortical, optic nerve, subretinal, and epiretinal). Visual loss caused by outer retinal degeneration in diseases such as retinitis pigmentosa or age-related macular degeneration can be reversed by electrical stimulation of the retina or the optic nerve (retinal or optic nerve prostheses, respectively). On the other hand, visual loss caused by inner or whole thickness retinal diseases, eye loss, optic nerve diseases (tumors, ischemia, inflammatory processes etc.), or diseases of the central nervous system (not including diseases of the primary and secondary visual cortices) can be reversed by a cortical visual prosthesis. The intent of this article is to provide an overview of current and future concepts of retinal and optic nerve prostheses. This article will begin with general considerations that are related to all or most of visual prostheses and then concentrate on the retinal and optic nerve designs. The authors believe that the field has grown beyond the scope of a single article so cortical prostheses will be described only because of their direct effect on the concept and technical development of the other prostheses, and this will be done in a more general and historic perspective.. ( Surv Ophthalmol 47 :335-356, 2002.
Raman spectroscopy iris endophthalmitis uveitis differential diagnosis principal components analy... more Raman spectroscopy iris endophthalmitis uveitis differential diagnosis principal components analysis Mahalanobis distance discriminant analysis a b s t r a c t
To evaluate histopathological retinal and renal response after one single dose of intravitreous i... more To evaluate histopathological retinal and renal response after one single dose of intravitreous injection of antiangiogenic drugs ranibizumab and bevacizumab in rats. Experimental study in 60d of life adults Wistar rats. Ten animals were included. Group 1 included 5 animals that were injected with 1 µL ranibizumab 1.25 mg in the right eye and with 1 µL of balanced salt solution (BSS) in the left eye, as control; Group 2 included 5 animals that were injected with 1 µL of bevacizumab in the right eye and with 1 µL of BSS in the fellow eye. All injections were performed with Hamilton syringes. After 15d of the interventions, all animals were sacrificed in CO2 chamber. Both eyes were enucleated and one kidney was removed, fixed and embedded in paraffin for histopathological analysis by optic microscopy. For statistical purposes the initial expected abnormal histopathological responses were defined as 0%. Atypical histopathological retinal response was detected in 2 eyes injected with ra...
IEEE Transactions on Neural Systems and Rehabilitation Engineering, 2006
Experiments were conducted to assess the effect of stimulating electrode parameters (size, positi... more Experiments were conducted to assess the effect of stimulating electrode parameters (size, position, and waveform shape) on electrically elicited ganglion cell action potentials from isolated rabbit retina. Thirty-eight isolated rabbit retinas were stimulated with bipolar stimulating electrodes (either 125 or 25 mum in diameter) positioned on either the ganglion or the photoreceptor side. Recording electrodes were placed between the optic
Data comparing systemic exposure and systemic vascular endothelial growth factor (VEGF) suppressi... more Data comparing systemic exposure and systemic vascular endothelial growth factor (VEGF) suppression of ranibizumab, bevacizumab and aflibercept following intravitreal injection are lacking. Fifty-six patients with wet age-related macular degeneration received intravitreal ranibizumab (0.5 mg), bevacizumab (1.25 mg), or aflibercept (2.0 mg). Serum pharmacokinetics and plasma free VEGF were evaluated after the first and third injections. Following the first dose, systemic exposure to aflibercept was 5-, 37-, and 9-fold higher than ranibizumab, whereas, bevacizumab was 9-, 310-, and 35-fold higher than ranibizumab, based on geometric mean ratio of peak and trough concentrations and area under the curve, respectively. The third dose showed accumulation of bevacizumab and aflibercept but not ranibizumab. Aflibercept substantially suppressed plasma free VEGF, with mean levels below lower limit of quantitation (10 pg/mL) as early as 3 h postdose until ≥7 days postdose. Mean free (unbound) ...
Retina-the Journal of Retinal and Vitreous Diseases, 2002
Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for RETINA. Enter you... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for RETINA. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your ...
To report the clinical, electrophysiologic, and histologic findings of different concentrations o... more To report the clinical, electrophysiologic, and histologic findings of different concentrations of indocyanine green (ICG) injected into the vitreous cavity of rabbit eyes. Forty-two rabbits underwent intravitreal injection of 0.1 mL of ICG in three different concentrations: 0.5 mg/mL (250 mOsm), 5 mg/mL (270 mOsm), and 25 mg/mL (170 mOsm). Fellow eyes were injected with 0.1 mL of balanced salt solution. Biomicroscopy, ophthalmoscopy, electroretinography, fluorescein angiography, and histologic evaluation were performed. Eyes injected with 0.5 mg/mL of ICG showed b-wave latency delay on the first day after injection. Eyes injected with 5 mg/mL of ICG showed b-wave latency delay and decreased b-wave amplitude on the first and seventh days after injection; delayed a-wave latency on the first day after injection was also observed. Eyes injected with 25 mg/mL of ICG showed b- and a-wave amplitude and latency abnormalities during the entire follow-up. Direct correlation of increasing ret...
To evaluate the effects of indocyanine green (ICG) injection on the retinal surface and into the ... more To evaluate the effects of indocyanine green (ICG) injection on the retinal surface and into the subretinal space of rabbit eyes. Twenty-two Dutch-belted rabbits underwent two-port vitrectomy followed by injection of ICG (5 mg/mL) on the retinal surface and into the subretinal space. Balanced salt solution (BSS) was also injected subretinally. The locations where ICG was delivered (both epiretinal and subretinal) were exposed to light from an endoilluminator for 7 minutes. The animals were examined at 1, 7, and 14 days after surgery. The eyes were studied by fluorescein angiography as well as light and electron microscopy. No damage was observed after epiretinal ICG injection, but subretinal ICG injection resulted in damage to the outer nuclear layer, photoreceptor inner and outer segments, and retinal pigment epithelium. This damage was more severe with longer follow-up. Control experiments without ICG, in which balanced salt solution was injected into the subretinal space or light...
... MAIA, MAURICIO MD; HALLER, JULIA A. MD; PIERAMICI, DANTE J. MD; MARGALIT, EYAL MD, PhD; DE JU... more ... MAIA, MAURICIO MD; HALLER, JULIA A. MD; PIERAMICI, DANTE J. MD; MARGALIT, EYAL MD, PhD; DE JUAN, EUGENE JR. ... Baltimore, Maryland, USA; the Doheny Retina Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA ...
Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leadin... more Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leading cause in the population between 20 and 60 years old. Among patients with DR, diabetic macular edema (DME) is the most frequent cause of vision impairment and represents a significant public health issue. Macular photocoagulation has been the standard treatment for this condition reducing the risk of moderate visual loss by approximately 50%. The role of vascular endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated in recent studies. This review addresses and summarizes data from the clinical trials that investigated anti-VEGF for the management of DME and evaluates their impact on clinical practice. The literature searches were conducted between August and October 2013 in PubMed and Cochrane Library with no date restrictions and went through the most relevant studies on pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. The eff...
To investigate the histologic and clinical effects of subretinal injection of patent blue (PB) an... more To investigate the histologic and clinical effects of subretinal injection of patent blue (PB) and trypan blue (TB) in rabbits. Dutch-belted rabbits (n=8) were vitrectomized followed by subretinal injection of 2.4 mg/ml PB (285 mOsm) and 1.5 mg/ml TB (312 mOsm); balanced salt solution (BSS) (300 mOsm) served as the control. Animals were examined 6, 12, and 24 hr and 14 days after the procedure by fluorescein angiography (FA) and indirect ophthalmoscopy; for retinal toxicity, histologic evaluation studies were performed by light and transmission electron microscopy. FA examination demonstrated window defects suggestive of retinal pigment epithelium (RPE) atrophy in positions of subretinal TB injection, but this was not observed after subretinal injection of PB or BSS. Histologic evaluation disclosed only minimal abnormalities on the photoreceptor outer segment (POS) after subretinal injection of BSS during all follow-up. Subretinal injection of PB caused POS and photoreceptor inner s...
To investigate the retinal biocompatibility of Brilliant Blue G with deuterated water (BBG-D2O) a... more To investigate the retinal biocompatibility of Brilliant Blue G with deuterated water (BBG-D2O) as a vital dye for chromovitrectomy. In this animal study, 0.05 mL of 0.25 g/L Brilliant Blue G (BBG) associated with 0.13 mL/mL of deuterium oxide (D2O) was injected intravitreally in the right eye and the same amount of balanced salt solution (BSS) was injected similarly in the left eye of rabbits. Clinical examination and histology with light microscopy were performed after seven days. Retinal cell layers were evaluated for morphologic alterations. Electroretinographic (ERG) changes were also assessed at baseline and 7 days after the injections. A total of 6 rabbits were included in the study. The gross histopathologic appearance of the retina, choroid, sclera and optic nerve was within normal limits without any sign of severe retinal necrosis or cystic degeneration. Light microscopy showed that BBG-D2O caused no substantial alterations in retinal layers as compared to control eyes. Th...
Investigative ophthalmology & visual science, Jan 19, 2015
Purpose: To investigate and compare the mechanism by which lutein-based and synthetic intraocular... more Purpose: To investigate and compare the mechanism by which lutein-based and synthetic intraocular dyes interact with their target membranes during ophthalmic surgeries. Methods: Surrogate membrane models were used in order to simulate the different intraocular membranes: internal limiting membrane (ILM), vitreous, anterior capsule (AC) and epiretinal membrane (ERM). Different lutein-based dyes, such as Phacodyne, Retidyne, Retidyne Plus and Vitreodyne were tested, as well as Trypan Blue (TB), Indocyanine Green (ICG), Brilliant Blue (BB) and Triamcinolone Acetonide (TA). The interactions between the film components occurring at the air-water interface were investigated with surface pressure-area isotherms and polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS). Results: With the exception of TA and ICG, none of the tested dyes revealed toxicity to the analyzed membranes. The interaction of TA with the vitreous model affected deeply the biointerface structur...
To describe the systemic pharmacokinetics of ranibizumab after intravitreal administration in pat... more To describe the systemic pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion (RVO) or diabetic macular edema (DME). A population approach of nonlinear mixed-effect pharmacokinetics modeling based on serum concentrations of ranibizumab measured at various times after intravitreal administration. Patients with RVO (n = 441) and DME (n = 435) from 4 large, randomized, phase 3 clinical trials of monthly ranibizumab intravitreal administration. A 1-compartment pharmacokinetics model with first-order absorption and elimination rate constants previously developed in patients with age-related macular degeneration (AMD) was fitted separately to RVO and DME data. Population pharmacokinetic parameters and interindividual variability were estimated for each model. Baseline covariates were evaluated for potential effects on systemic pharmacokinetics. Model performance was validated using general diagnostic plots and a visual predictive check. Ranibizumab disposition was determined in RVO and DME patients and compared with that previously seen in AMD patients. The AMD pharmacokinetics model correctly predicted the measured serum ranibizumab concentration data for RVO and DME patients. Most observed data points were within the simulated 90% confidence interval, indicating that systemic ranibizumab concentrations were comparable among AMD, RVO, and DME patients. No disease-related covariates were identified by the population pharmacokinetics analysis. The systemic pharmacokinetics of ranibizumab were similar among patients with AMD, RVO, or DME. Disease-related differences and patient demographics, measured in this study, did not lead to variability in ocular elimination or in systemic exposure of ranibizumab after intravitreal administration. In all disease processes tested, ranibizumab exits the eye slowly and then is eliminated rapidly from the circulation, thus minimizing systemic exposure.
We report a case of a 19-year-old woman presenting bilateral neurosensorial hearing loss, mental ... more We report a case of a 19-year-old woman presenting bilateral neurosensorial hearing loss, mental abnormalities, and loss of visual field in the left eye. Visual acuity was 20/20 in OD and 20/25 in OS. Patient was examined systemically. Audiometry showed sensorineural hearing loss in both ears. The magnetic resonance imaging (MRI) of brain revealed multiple small lesions in the white matter in both cerebral hemispheres and at the corpus callosum. Fundoscopy showed bilateral normal optic disc and sheathing of the arterioles in the middle periphery of OD. Retinal edema and cotton-wool spots were observed. Fluorescein angiography showed bilateral peripheral occlusive arterial vasculopathy. The patient was diagnosed with Susac syndrome and treated with quetiapine fumarate, flunitrazepam, and prednisone, which resulted in stabile outcome. This case shows that a high index of suspicion leading to early recognition and treatment is important to avoid irreversible damage.
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Papers by Mauricio Maia