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To determine whether early visual acuity response to intravitreal dexamethasone implant therapy in diabetic macular edema (DME) is associated with long-term outcome.Retrospective case series.Multicenter (8 sites) retrospective review of medical records of eyes with DME treated with 0.7 mg intravitreal dexamethasone implant and minimum 18-month follow-up. One hundred and two eyes were included. Eyes with vitreoretinal interface abnormalities or that had undergone vitrectomy were excluded. Eyes were categorized into 3 groups based on change in best-corrected visual acuity (BCVA) at 3 months (logMAR equivalence of5-letter, 5-9-letter, or ≥10-letter gain). Visual acuity outcomes were determined for each early response group. The relationship between early (3-month) and overall change in BCVA was assessed using regression analysis.In the study population (102 eyes),5-letter, 5- to 9-letter, and ≥10-letter BCVA improvements were seen in 44.1%, 18.6%, and 37.3% of eyes, respectively, at 3 months. Among suboptimal (5-letter) responders at 3 months, 6.7% showed ≥10-letter gains at study conclusion compared to 29% in the robust (≥10-letter) early response group (P = .009). Change in BCVA at 3 months showed significant positive correlation with overall change in BCVA (coefficient = 0.44, P = .002).A similar proportion of eyes demonstrated suboptimal (5-letter) and robust (≥10-letter) early response to treatment at 3 months. Eyes with a robust early response demonstrated ≥10-letter long-term gain in BCVA at a significantly higher rate compared to those with poor early response. Early treatment response directly correlated with overall change in BCVA.

Evaluate toxicity of acai fruit (Euterpe oleracea) dye concentrations in a rabbit model.Rabbits were injected intravitreously with 10%, 25%, and 35% acai dye concentrations. Control eyes received balanced salt solution (BSS). Electroretinogram (ERG), fundus imaging, fluorescein angiography (FA), optical coherence tomography (OCT), and light and transmission electron microscopy (LM/TEM) were performed.Fundus imaging showed increased vitreous opacity with increased dye concentrations. FA and OCT showed normality with all concentrations. Comparisons between BSS and dye concentrations were analyzed using Kruskal-Wallis and Mood's median test (p0.05). At 24 h, ERGs showed reduced amplitudes from baseline in all eyes. Median b-wave amplitudes nonsignificantly decreased and latency increased with 10% and 25%; findings were significant (p0.05) for 35%. LM and TEM showed no abnormalities for 10% and 25%. With 35%, TEM showed ganglion cell edema at 24 h that resolved after 7 days. Vacuolization, multilamellar bodies, and nerve bundle damage occurred at 24 h/7 days in the inner nuclear layer. Mitochondrial cristae disruption occurred in the inner photoreceptor segment at 24 h that decreased by 7 days.Ten and twenty-five percent concentrations were safe and may improve identification of the posterior hyaloid and internal limiting membrane during chromovitrectomy in humans.

Purpose: To report the fundus manifestations and spectral-domain optical coherence tomographic (SD-OCT) features of dengue fever presenting as Purtscher-like retinopathy.Methods: Retrospective review of two cases of dengue fever.Results: Color fundus photograph revealed the presence of cotton-wool spots in a Purtscher-like configuration in the posterior pole of all study eyes. SD-OCT demonstrated increased reflectivity signal in the inner retinal layers, and after a variable follow-up period, there was complete disappearance of cotton-wool spots and persistence of the hyperreflectivity signal.Conclusion: We report two unique cases of dengue fever associated with retinal lesions in a configuration of Purtscher-like retinopathy.

Ziv-aflibercept (Zaltrap® ), a recombinant fusion protein that binds diffusible vascular endothelial growth factor (VEGF), is approved for the treatment of metastatic colorectal carcinoma. Its molecular structure is the same as aflibercept (Eylea® ), thus making it an attractive option for the off-label treatment of chorioretinal vascular conditions. Ziv-aflibercept is distributed in 4 and 8 ml vials for intravenous use, and its cost after compounding is similar to bevacizumab. Studies with retinal pigment epithelium cytotoxicity, animal histologic sections and electroretinography have demonstrated its safety, and mathematical modelling combined with over four dozen clinical publications from different ophthalmic centres throughout the world attest to its efficacy. No appreciable differences in visual or anatomic outcomes between 1.25 mg (0.05 ml) and 2.5 mg (1.0 ml) doses have been noted. The long duration of action combined with the low cost make ziv-aflibercept an attractive anti-VEGF treatment option, especially in low- and middle-income countries where its popularity is increasing.

Background To evaluate the benefits of lutein in preventing retinal phototoxicity generated by xenon light sources during vitreoretinal surgery. Methods A prospective cross-sectional study in pigmented rabbit eyes exposed to different vitreoretinal surgery lighting simulations. Twenty Dutch-belted rabbits were divided into two groups exposed to two different xenon wavelength light sources filters (420 nm and 435 nm). In addition, two subgroups were administered with daily supplemental of 10 mg of Lutein systemically. Electroretinography (ERG), optical coherence tomography (OCT) and fluorescein angiography (FA) were performed before and after surgery to quantify the retinal damage. Results All animals submitted to the experiment presented some degree of phototoxicity independent of wavelength light filter used. Retinal damage was evident as the FA presented areas of hyperfluorescence, and the OCT depicted increased reflective areas of the inner and outer retinal layers, and RPE. ERG showed a diffuse reduction of the a and b waves amplitudes in all animals. Conclusion Use of systemic administration of lutein showed no benefit to avoiding retinal phototoxicity generate to xenon light source using filters of 435 nm and 420 nm when comparing to the control group.

BACKGROUND AND OBJECTIVE: To report a unique case series of diffuse unilateral subacute neuroretinitis (DUSN) patients imaged with optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: In this retrospective case series, multimodal imaging was performed in four patients with DUSN at the time of patient visit. The study patients underwent standard clinical treatment for DUSN. RESULTS: The clinical findings were consistent with the diagnosis of DUSN. Cross-sectional OCT showed disruption of outer retinal layers in the foveal area and an irregular structure of the outer plexiform layer. En face OCT revealed hyperreflective spots and a large hyperreflective lesion in the foveal area correspondent to the outer retina disruption seen on cross-sectional OCT. OCTA demonstrated decreased vascular perfusion in both the superficial and deep retinal capillary plexuses along with choriocapillaris preservation. CONCLUSION: OCTA may provide a more detailed assessment of the retinal microvascular changes, allowing a more precise anatomical-functional correlation in DUSN. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:76–83.]

Purpose: To study the efficacy and safety of treatments with ranibizumab and bevacizumab for exudative age-related macular degeneration. Methods: A parallel randomized clinical trial was conducted to compare the efficacy and safety of three regimens (bevacizumab every month, bevacizumab every 2 weeks, and ranibizumab every month), followed by as-needed retreatments, for 1 year, in previously untreated individuals with age-related macular degeneration. The primary outcome was change in visual acuity and in central macular thickness after 1 year of follow-up. Subjects were assigned randomly to one of the three groups in a 1:1:1 ratio, and investigators and examiners were blinded to the randomization results. Results: We included 15 patients in each group. After 1 year of follow-up, we found statistically significant improvements in visual acuity and central macular thickness reduction in all groups. However, we found no statistically significant differences between the three groups. Conclusions: The bi-weekly follow-up was effective and we found no significant differences in efficacy or safety between the treatments with ranibizumab and bevacizumab. RESUMO Objetivo: Estudar a eficácia e segurança dos tratamentos com ranibizumabe e bevacizumabe para a degeneração macular relacionada à idade exsudativa. Métodos: Ensaio clínico paralelo randomizado foi conduzido para comparar a eficácia e segurança de três regimes (bevacizumabe a cada mês, bevacizumabe a cada 2 semanas e ranibizumabe todos os meses), seguidos por retratamentos conforme necessidade, durante 1 ano, em indivíduos previamente não tratados com degeneração macular relacionada à idade. O desfecho primário foi alteração na acuidade visual e na espessura macular central após um ano de seguimento. Os indivíduos foram designados aleatoriamente para um dos 3 grupos em uma proporção de 1:1:1, e os investigadores e examinadores foram mascarados para os resultados da randomização. Resultados: Foram incluídos 15 pacientes em cada grupo. Após um ano de seguimento, encontramos melhorias estatisticamente significativas na acuidade visual e na redução da espessura macular central em todos os grupos. No entanto, não encontramos diferenças estatisticamente significativas entre os 3 grupos. Conclusões: O seguimento quinzenal foi eficaz e não encontramos diferenças significativas na eficácia ou segurança entre os tratamentos com bevacizumabe e ranibizumabe.

Background To evaluate the efficacy of selective episcleral delivery of celecoxib formulated in a sustained-release episcleral exoplant on a model of retinal and choroidal neovascularization induced in rabbits by subretinal injection of matrigel combined with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Methods Nine New Zealand white rabbits were randomly assigned to three groups (episcleral celecoxib exoplant, intravitreal bevacizumab injection and control group). The bFGF was mixed with matrigel at a concentration of 10 ug/0.1 mL, and VEGF was mixed with matrigel at a concentration of 2 ug/0.1 mL. Animals assigned to celecoxib or intravitreal bevacizumab groups were treated within 03 days from matrigel injection. Fluorescein angiography (FA) and electroretinography (ERG) were performed 5 days, 2, 4 and 8 weeks after matrigel injection. Persistence or regression of three clinical features (subretinal hyperfluorescence, retinal vascular tortuosity and retinal fibrotic spots) was independently evaluated in each study group at all follow-up periods. Statistical analysis using Fisher’s exact test was performed to compare the frequency of findings at each time point between treated groups and control. Results In all study eyes, matrigel induced the appearance of subretinal blebs and the development of retinal and subretinal neovascularization characterized by progressive and late hyperfluorescence on FA. Persistence of subretinal hyperfluorescence was higher in non-treated (control) animals compared to celecoxib (p = 0.0238) treated animals. The mean b-wave amplitude ratios of ERG recordings did not reveal statistically significant differences between the study groups. Control animals retained in average 40% (± 7%) of the pre-treatment recorded b-wave amplitude, compared to 53% (± 29%) after bevacizumab and 53% (± 17%) after celecoxib treatment. Conclusion In this rabbit model of retinal and subretinal neovascularization, episcleral celecoxib delivery was demonstrated to significantly inhibit neovascularization. It was also noticed, although not statistically significant, an apparent effect of episcleral celecoxib on preventing tractional retinal detachment secondary to epiretinal fibrovascular proliferation. The transscleral delivery of celecoxib combined with sustained-release strategy may have impact in the treatment of retinal and choroidal proliferative diseases.

Background/aimsTo assess silicone oil (SO) release by different brands of syringes used for intravitreal injection under different handling conditions.MethodsEight syringes were analysed: from the USA, Terumo 0.5 mL, Becton-Dickinson (BD) Tuberculin 1 mL, BD Luer-lok 1 mL, BD Ultra-Fine 0.3 mL and Exel Insulin 0.3 mL; from Germany, Braun Omnifix-F 1 mL and Braun Injekt-F 1 mL and from Spain, BD Plastipak 1 mL. The impact of air, priming the plunger, agitation by flicking and fluid temperature on SO release were assessed by light microscopy. Fourier transform infrared spectroscopy (FTIR) was performed to identify the molecular compound in each syringe.ResultsFive hundred and sixty syringes were analysed. Terumo 0.5 mL and BD Ultra-Fine 0.3 mL released more SO than all others. BD Luer-lok 1 mL, BD Plastipak and Braun Omnifix-F 1 mL released little SO; BD Tuberculin 1 mL, Exel 0.3 mL and Braun Injekt-F 1 mL released the least SO. Priming the syringe and different temperatures did not significantly affect SO release. Agitation by flicking caused a significantly higher proportion of samples to have SO droplets and an increased number of oil droplets. Air had an additive effect on the release of oil in the agitation groups. FTIR identified polysiloxane in all syringes but Injekt-F.ConclusionSyringes commonly used for intravitreal injections frequently release SO droplets, especially when agitated by flicking. To avoid unnecessary ocular risks, syringes should not be agitated before intravitreal injection. It is desirable that syringes be manufactured specifically for ophthalmic use.

Diabetic macular edema is the leading cause of blindness in young adults in developed countries. Beyond metabolic control, several therapies have been studied such as laser treatment and intravitreal injections of corticosteroids or anti-vascular endothelial growth factor drugs. In terms of public health the long-term treatment with the current available drugs is very expensive and new therapies with the same or better effect should be investigated. This study sought to evaluate the efficacy and safety of intravitreal injections of ziv-aflibercept for the treatment of diabetic macular edema.Seven consecutive patients with diabetic macular edema were enrolled. A complete examination, including full-field electroretinography, visual acuity, central retinal thickness, and evaluation of systemic and ocular complications, was performed before and at 24 weeks after intravitreal injections of ziv-aflibercept. The seven patients were submitted to six consecutive intravitreal injections of ziv-aflibercept with a 4-week interval.No significant differences were found in the amplitude or implicit time of any electroretinography component after intravitreal injections of ziv-aflibercept, and no systemic or ocular complication was observed. The improvement of visual acuity was significant at 24 weeks (P0.05). The central retinal thickness significantly decreased during the course of 24 weeks.Intravitreal injections of ziv-aflibercept seem to be a safe and effective treatment option for diabetic macular edema.

Purpose: The aim of this study was to access the safety profiles of 2 fusion proteins with anti-vascular endothelial growth factor action (ziv-aflibercept and aflibercept) on retinal pigment epithelium cells and Muller-Glia cells in culture by assessing cell viability post drug exposure. Methods: Primary human retinal pigment epithelium cells (pRPE) and Muller-Glia cells (Mio-M1) were exposed to the clinical standardized concentrations of ziv-aflibercept (25 mg/mL) and aflibercept (40 mg/mL). Progressively higher concentrations of NaCl (300, 500, 1,000, 1,500, 2,000, 5,000, and 10,000 mosm/kg) were also applied to cells to assess the possibility of potentiating hyperosmotic cytotoxity effect. The study was applied to measure pRPE and Mio-M1 viability by a tetrazolium dye-reduction assay (XTT). Results: Cell viability of both pRPE and Mio-M1 presented no significant changes after exposure of ziv-aflibercept and aflibercept. Progressive NaCl concentrations did not significantly alter cell viability. The exposure to the negative control of 75 µL/mL of dimethyl sulfoxide showed significant reduction in cell viability. Conclusions: At clinical doses, neither ziv-aflibercept nor aflibercept caused any significant reduction in cell viability in vitro. Furthermore, injection solutions of NaCl with higher osmolality caused no significant reduction in cell viability.

Purpose. To evaluate the best-corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of dexamethasone implants needed to treat cystoid macular edema (CME) from various etiologies over 12 months in vitrectomized and nonvitrectomized eyes.Methods. This multicenter retrospective cohort study included 112 patients with CME secondary to retinal diseases treated pro re nata (PRN) with a 0.7 mg intravitreal dexamethasone implant for 12 months. The BCVA, CRT, adverse events, safety data, and number of implants were recorded.Results. Vitrectomized and nonvitrectomized eyes received means of three implants and one implant, respectively, over 12 months (P<0.001). The mean BCVA of all patients improved from 0.13 at baseline to 0.33 (P<0.001) 12 months after one (P=0.001), two (P=0.041), and three (P<0.001) implants but not four implants (P=0.068). The mean baseline CRT decreased significantly (P<0.001) from 463 to 254 microns after 12 months with one (P<0.001), two (P=0.002), and three (P=0.001) implants but not with four implants (P=0.114). The anatomic and functional outcomes were not significantly different between vitrectomized and nonvitrectomized eyes. Increased IOP was the most common adverse event (23.2%).Conclusions. Dexamethasone implant administered PRN improved VA and decreased CRT in CME, with possible long-term clinically relevant benefits for treating CME from various etiologies. Vitrectomized eyes needed more implants compared with nonvitrectomized eyes.

Univ Fed Sao Paulo, Dept Ophthalmol, Rua Jacques Felix 278-54, BR-04509001 Sao Paulo, SP, Brazil

To investigate the binding affinity, stability, and sterility of aflibercept and ziv-aflibercept to vascular endothelial growth factor (Holash et al. in Proc Natl Acad Sci USA 99(17):11393–11398, 2002. https://doi.org/10.1073/pnas.172398299 ) after compounding and storage for up to 28 days at 4 °C and − 8 °C. Tuberculin-type 1-mL syringes were prepared containing aflibercept (40 mg/mL) and ziv-aflibercept (25 mg/mL). Samples were stored at 4 °C and − 8 °C for 0, 14, and 28 days and evaluated for the binding affinity of anti-VEGF to VEGF and stability using enzyme-linked immunosorbent assays. The evaluation of sample sterility was performed. Laboratory trials with aflibercept and ziv-aflibercept showed preservation of the drug-binding capability to recombinant VEGF when stored in plastic syringes for up to 28 days at 4 °C and − 8 °C. No significant decrease in mass or concentration were observed. Microbiologic evaluations did not detect contamination in the syringes. The current study corroborates that compounded anti-VEGF drugs aflibercept and ziv-aflibercept do not loose stability or binding affinity and do not become contaminated if prepared under sterile conditions and stored at 4 °C or − 8 °C for 14 or 28 days.

Background Swept-source optical coherence tomography (SS-OCT) has a higher scanning rate and longer wavelength in comparison with spectral-domain OCT (SD-OCT), allowing an improved imaging of retinal vascular plexuses and choriocapillaris. The present two patients diagnosed with multiple evanescent white dot syndrome (MEWDS) underwent fundus autofluorescence (FAF), en-face SS-OCT, and SS-OCT angiography (OCTA) imaging, and its features were described and correlated. Results The clinical and imaging findings of both cases were consistent with the diagnosis of MEWDS. Color fundus photograph revealed subtle deep retinal white spots in the posterior pole and around the optic disk. FAF showed several hyperautofluorescent lesions corresponding topographically to the subtle deep retinal white lesions observed on color fundus photographs. Cross-sectional SS-OCT showed disruption of the ellipsoid zone (EZ) within the macular area in all study patients. En-face SS-OCT at the level of the outer retina showed lower reflectivity correspondent to the diffuse attenuation due to the EZ disruption on cross-sectional OCT. SS-OCTA demonstrated flow preservation within the retinal vasculature and choriocapillaris. Conclusions SS-OCT imaging allows a better visualization of the choriocapillaris, and its normal appearance in MEWDS may suggest that the outer retina and photoreceptors represent the primary site of inflammation.

To test the applicability of the acai dye at a 25% concentration for identifying the posterior hyaloids and internal limiting membranes (ILMs) during pars plana vitrectomy (PPV) in human eyes with macular holes (MHs). This study included 25 patients with chronic idiopathic MHs. The exclusion criteria included glaucoma, previous significant ocular conditions, and previous ocular surgeries except uncomplicated cataract. Ten surgeons performed 23-gauge four-port PPV, phacoemulsification, posterior hyaloid detachment, ILM peeling guided by dye staining, and perfluoropropane injection. The patients remained prone for 5 days postoperatively. The patients were evaluated postoperatively after 1, 30, and 180 days. The surgeons completed a questionnaire regarding the dye’s staining abilities. The posterior hyaloids and ILMs stained purple in all eyes. The final best-corrected visual acuity improved significantly (p

To compare surgeons’ opinions regarding idiopathic full-thickness macular hole (MH) surgery by using traditional microscopy and three-dimensional (3-D) visualization system. To analyze the required time for pars plana vitrectomy (PPV) and for internal limiting membrane (ILM) rhexis by using both visualization methods. To evaluate anatomical surgical results. Four surgeons (surgeon 1, fellows 1, 2, 3) performed the total of 40 surgeries for treating MHs. Each one performed 10 surgeries (5 with traditional microscopy and 5 with 3-D visualization). The completion time for PPV and ILM rhexis was determined by using both methods. Ergonomics, educational value, image sharpness, depth perception, field of view and technical skills were analyzed through answering a questionnaire. Forty patients were included in the study. The MH size for surgeon 1, fellows 1, 2 and 3 groups, individually, ranged from 237 to 602 μm; 228 to 590 μm, 271 to 611 μm and 289 to 600 μm, respectively. In the 3-D and in the traditional microscopy subgroups (which includes all 4 physicians on the use of one or the other method), the MH size ranged from 228 to 602 μm and 237 to 611 μm, respectively. Comparisons between the average time for full PPV and ILM rhexis by using the two methods were non-significant, neither in each individual case of 3-D surgery for each surgeon. Surgeon 1 had always been faster than his fellows. Depth perception was rated as similar for both methods. Field of view and educational values were rated as superior when using the 3-D system. Image resolution and ergonomics were rated as superior when using traditional microscopy. Technical skills strongly tended toward ‘superiority’ when using traditional microscopy. Thirty-six (90%) full-thickness MHs were successfully closed with one surgery. The 3-D system for MH surgery had a short learning curve and was a refined educational tool, when used with reduced illumination and precise focus. Concerning MH surgery, heads-up method was similar to traditional microscopy regarding length of time and anatomical surgical results. Heads-up surgery may become a new pattern for ophthalmic surgery as ongoing improvements are applied.

Objective: To compare two different laser strategies of panretinal photocoagulation for diabetic retinopathy. Methods: Single-center, randomized study including 41 eyes treated with 577-nm multispot laser with a 20-ms pulse duration (group 1) or a 532-nm single-spot laser with a 100-ms pulse duration (group 2). The outcomes included best-corrected visual acuity (BCVA) and imaging changes at baseline, 6 and 12 months, laser parameters, and results of subjective pain analysis. Results: At 12 months, the treatments did not differ significantly in BCVA, central retinal thicknesses (CRTs), improved macular edema, vitreomacular interface changes, patient-reported pain scores, or angiographic responses. Group 1 had significantly fewer treatment sessions but used more laser spots (p < 0.001). Conclusion: The multispot laser required fewer applications with more spots delivered to compensate for lower fluency, showing similar patient tolerance to single-spot laser. Both groups maintained the initial visual acuities and CRTs; about 50% of cases had vitreomacular interface changes and improved macular edema, with similar angiographic improvements after 12 months.

Background To evaluate the efficacy of selective episcleral delivery of celecoxib formulated in a sustained-release episcleral exoplant on a model of retinal and choroidal neovascularization induced in rabbits by subretinal injection of matrigel combined with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Methods Nine New Zealand white rabbits were randomly assigned to three groups (episcleral celecoxib exoplant, intravitreal bevacizumab injection and control group). The bFGF was mixed with matrigel at a concentration of 10 ug/0.1 mL, and VEGF was mixed with matrigel at a concentration of 2 ug/0.1 mL. Animals assigned to celecoxib or intravitreal bevacizumab groups were treated within 03 days from matrigel injection. Fluorescein angiography (FA) and electroretinography (ERG) were performed 5 days, 2, 4 and 8 weeks after matrigel injection. Persistence or regression of three clinical features (subretinal hyperfluorescence, retinal vascular tortuosity and retinal fibrotic spots) was independently evaluated in each study group at all follow-up periods. Statistical analysis using Fisher’s exact test was performed to compare the frequency of findings at each time point between treated groups and control. Results In all study eyes, matrigel induced the appearance of subretinal blebs and the development of retinal and subretinal neovascularization characterized by progressive and late hyperfluorescence on FA. Persistence of subretinal hyperfluorescence was higher in non-treated (control) animals compared to celecoxib (p = 0.0238) treated animals. The mean b-wave amplitude ratios of ERG recordings did not reveal statistically significant differences between the study groups. Control animals retained in average 40% (± 7%) of the pre-treatment recorded b-wave amplitude, compared to 53% (± 29%) after bevacizumab and 53% (± 17%) after celecoxib treatment. Conclusion In this rabbit model of retinal and subretinal neovascularization, episcleral celecoxib delivery was demonstrated to significantly inhibit neovascularization. It was also noticed, although not statistically significant, an apparent effect of episcleral celecoxib on preventing tractional retinal detachment secondary to epiretinal fibrovascular proliferation. The transscleral delivery of celecoxib combined with sustained-release strategy may have impact in the treatment of retinal and choroidal proliferative diseases.

Purpose To describe the visual, tomographic, and electroretinographic findings in a patient with macular edema secondary to branch retinal vein occlusion who was submitted to three consecutive intravitreal injections of ziv-aflibercept. Methods The patient underwent a complete ophthalmic examination, as well as optical coherence tomography and full-field electroretinography at baseline and 90 days after the first injection. Results The best-corrected visual acuity improved from 20/400 to 20/40, and the central retinal thickness decreased from 791 μm to 198 μm after three consecutive intravitreal injections of ziv-aflibercept. Full-field electroretinography showed an increase in cone amplitude and decrease in rod amplitude. No adverse side effects were observed after injections. Conclusion Intravitreal injections of ziv-aflibercept showed both effectiveness and safety in the treatment of a patient with macular edema secondary to branch retinal vein occlusion. The observed anatomic (by ophthalmic examination, optical coherence tomography) and functional (best-corrected visual acuity, full-field electroretinography) improvements and lack of serious adverse side effects demonstrates the potential of intravitreal injections of ziv-aflibercept for the treatment of macular edema secondary to branch retinal vein occlusion.

Purpose. To classify and quantify anthocyanins in a vital dye extracted from the acai fruit (Euterpe oleracea), adjust pH and osmolarity, and perform lyophilization to develop a new chromovitrectomy dye. Methods. Three dye concentrations 10%, 25%, and 35% (equivalent to 100, 250, and 350 mg of lyophilized acai fruit pulp extract samples) were evaluated when diluted in 1 ml of phosphate-buffered solution (pH 7 and 300 mOsm). The dye was analyzed by mass spectrometry and high-performance liquid chromatography (HPLC) to identify and quantify anthocyanins molecules. Results. The pH and osmolarity correction and lyophilization were performed without damaging the anthocyanin molecular structure. Mass spectrometry confirmed the presence of five anthocyanins in the three concentrations of the dye. Cyanidin-3-O-glucoside was the major anthocyanin found. HPLC showed that the concentration of anthocyanin was similar, independent of the dye concentration tested. Conclusions. Lyophilization and the correction of pH and osmolarity (7.00 and 300 mOsm, resp.) were performed successfully. Five anthocyanins are present in the dye from the acai fruit. The major anthocyanin is cyanidin-3-O-glucoside. Independent of the dye concentration tested, the anthocyanin concentration was similar. Standardized chemical characteristics of this new dye may allow its use during chromovitrectomy in humans.

PURPOSE To compare the efficacy of different concentrations of topical lidocaine gel with standard subconjunctival anesthesia. METHODS This was a prospective randomized controlled pilot study with 3 different groups. Group SC received subconjunctival lidocaine and proparacaine drops as needed during surgery. Group L2 received 2% lidocaine gel and group L5 received 5% lidocaine gel. Both lidocaine gel groups could receive another gel dose as needed during the procedure. The primary outcome was pain, which was experienced during and after surgery. The assessment was done using a 10-point linear analog scale at predetermined stages of surgery (1-first incision, 2-pterygium body excision, 3-conjunctival suturing, 4-immediate postoperative period after patching, and 5-assessment by a trained nurse in the absence of a surgeon after operation). RESULTS We enrolled 45 consecutive patients who underwent primary pterygium surgery. Statistical significance between groups was found in mean pain at administration (2.2 vs. 0.4 vs. 0.0 in SC, L2, and L5 groups, respectively, with P < 0.05). The number of reapplications of anesthetic drops did not differ between the groups. We found a correlation between reapplication of the anesthetic and pain at administration and duration of the procedure. CONCLUSIONS We demonstrated that the use of lidocaine gel at concentrations of 2% and 5% in pterygium surgery was as effective as subconjunctival injection of lidocaine in reducing intraoperative and postoperative pain, producing significantly less pain during initial administration of the anesthetic.

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. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:457–462.]

To determine the effects of lens status on the success rate of primary pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment using either perfluoropropane gas (C3F8) or silicone oil (SO) tamponade.A retrospective chart analysis was made of 97 eyes from 92 patients with rhegmatogenous retinal detachment with no proliferative vitreoretinopathy that were treated with primary 23-gauge PPV. Eyes included in this were phakic (n = 28), pseudophakic (n = 41), or phakic eyes subject to simultaneous phacoemulsification, intraocular lens implantation, and PPV during primary rhegmatogenous retinal detachment repair (n = 28). Tamponade at the end of PPV was with either C3F8 (n = 65) or SO (n = 32). Success was defined as retinal reattachment at 1 year follow-up after a single procedure in eyes submitted to C3F8 injection; in eyes treated with SO injection, the success rate was defined as retina reattached 1 year after oil removal. Statistical comparisons were made between groups using chi-square, Fisher's exact test, Kruskal-Wallis, Mann-Whitney, and multivariate analysis. All eyes were operated by 2 experienced retina surgeons and had a minimum follow-up of 12 months.The vitreoretinal redetachment rate in eyes subjected to C3F8 tamponade was significantly higher (28.6%) for phakic eyes (P = 0.011) compared with pseudophakic or phakic eyes that underwent to phacoemulsification and intraocular lens implantation (4.5%). Eyes in which SO was used at the end of the surgical procedure demonstrated a similar trend of higher reoperation rates in phakic eyes (28.6%) compared with pseudophakic or phakic eyes (8%) subjected to phacoemulsification and intraocular lens implantation; however, no statistically significant difference was observed (P = 0.201). No statistically significant differences were found between groups in relation to the number of tears (P = 0.863) and their location (inferior: P = 0.189, superior: P = 0.708, nasal: P = 0.756, and temporal: P = 0.08).The success rates of primary 23-gauge PPV with either C3F8 or SO tamponade in pseudophakic eyes with rhegmatogenous retinal detachment was higher than the same procedure performed in phakic eyes. Still, the retrospective and limited data presented is too preliminary to suggest or recommend that practitioners perform simultaneous combined cataract surgery with retinal detachment and requires further studies in a larger and prospective design to confirm these present findings.

Vitrectomy is a surgery that involves complex and delicate techniques that treat diseases such as macular hole, epiretinal membrane and diabetic macular edema. Chromovitrectomy is one of these techniques and includes the use of coloring agents such as vital dyes or crystals to enhanced visibility of transparent structures during vitrectomy. The aim of this study was to present a modern approach, based on scientific evidence, about the application and indication of vital coloring agents during vitrectomy. The use of such agents has made this surgery more predictable and has increased its post-operative prognosis. Although research on chromovitrectomy is currently expanding there is still not an established gold standard dyeing agent.

To develop an experimental model of proliferative retinopathy by intravitreal injection of vascular endothelial growth factor 165 (VEGF165) in pigmented rabbits.A prospective, controlled, comparative intervention study. Six pigmented rabbits (Chinchilla breed) were subjected to intravitreal injection of VEGF165 in their right eye. The left eye was used as control and received an injection of balanced salt solution. In group 1, 3 rabbits received a 10-μg injection, and in group 2, 3 rabbits received a 20-μg injection. At baseline, all subjects were analyzed by anterior biomicroscopy, retinography, fluorescein angiography, and optical coherence tomography (OCT) fundus images. Biomicroscopy and all ancillary examinations were repeated at weeks 1, 2, and 5. In the fifth week after the injection, the rabbits were euthanized and the eyes were enucleated and subjected to histological evaluation.Seven days after the intravitreal VEGF165 injection, all rabbits developed intense neovascularization of the retina and anterior segment. Neovascularization of the posterior pole was similar in both groups, and the anterior segment was more florid in group 2. At weeks 1 and 2, neovascularization persisted with a minor decrease in conjunctival hyperemia in both groups. At week 5, there was a partial regression of neovascularization of the posterior pole, which was more prominent in group 1 than group 2, with persistent anterior neovascularization in both groups. OCT showed a statistically significant increase in retinal thickness, hyaloid detachment, and tractional retinal detachment. After the 5-week period, ocular histopathological evaluation showed an increase in retinal thickness, hyaloid detachment, and intense neovascularization in both groups, especially group 2.This pilot study of a neovascularization model using intravitreal injection of VEGF165 in pigmented rabbits showed that both doses of 10 and 20 μg were successful and effective in inducing vascular growth in the retina and anterior segment and can therefore be used for evaluating drug efficacy in future studies.

To report a unique case series of acute syphilitic posterior placoid chorioretinopathy (ASPPC) correlating en-face optical coherence tomography (OCT) with standard imaging modalities.In this retrospective case series, multimodal imaging was performed in three ASPPC patients at the time of disease presentation.Clinical and laboratory findings were consistent with the diagnosis of ASPPC. In all the study patients, multiple hyperreflective dot-like lesions distributed in the macular area and observed with en-face OCT at the level of retinal pigment epithelium (RPE) corresponded to the nodular RPE elevations on cross-sectional OCT and to the hyperautofluorescent spots on fundus autofluorescence. In addition, the cross-sectional OCT scans showed disorganization of the outer retinal bands and punctate choroidal hyperreflectivity.By combining en-face OCT with multimodal imaging analysis, we propose that a primary inflammation at the level of the choroid may be the pathogenic mechanism for the occurrence of outer retinal band abnormalities.

Background To report fluorescein angiography findings in a group of albuminuric Type 1 diabetes mellitus (T1DM) patients without diabetic retinopathy. Methods Fifteen albuminuric T1DM patients with normal/near normal estimated glomerular filtration rate without diabetic retinopathy underwent fluorescein angiography; presence of microaneurysms, vascular permeability changes and retinal malperfusion were evaluated. Results Fluorescein angiography revealed microaneurysms, blood-retinal barrier breakdown and retinal ischemia in 10 (67%) and 11 (73%); 8 (53%) and 9 (60%); 2 (13%) and 5 (33%) of patients at baseline and follow up, respectively. Follow up time averaged 24.6 months, minimum follow up time was 20 months. Patients who presented retinal malperfusion had higher HbA1C and lower estimated glomerular filtration rate. Conclusions Most albuminuric T1DM patients with a normal fundus exam had angiographic signs of diabetic retinopathy, some presenting retinal malperfusion. Retinal changes may be found with more sensitive testing in these patients, especially with impaired estimated glomerular filtration rate, even if the fundus exam is normal, and fluorescein angiography should be considered. These findings point to a homogenous presentation of the diabetic microangiopathies. Electronic supplementary material The online version of this article (10.1186/s40942-017-0102-y) contains supplementary material, which is available to authorized users.

Purpose: To report the incidence and clinical features of patients that experienced un-explained visual loss following silicone oil (SO) removal. Methods: Multicenter retrospective study of patients that underwent SO removal during 2000-2012. Visual loss of ≥2 lines was considered significant. Results: A total of 324 eyes of 324 patients underwent SO removal during the study period. Forty two (13%) eyes suffered a significant visual loss following SO removal. Twenty three (7.1%) of these eyes lost vision secondary to known causes. In the remaining 19 (5.9%) eyes, the loss of vision was not explained by any other pathology. Eleven of these 19 patients (57.9%) were male. The mean age of this group was 49.2 ± 16.4 years. Eyes that had an un-explained visual loss had a mean IOP while the eye was filled with SO of 19.6 ± 6.9 mm Hg. The length of time that the eye was filled with SO was 14.8 ± 4.4 months. In comparison, eyes that did not experience visual loss had a mean IOP of 14 ± 7.3 mm Hg (p < 0.0002) and a mean tamponade duration of 9.3 ± 10.9 months (p < 0.0001). Conclusions: An un-explained visual loss after SO removal was observed in 5.9% of eyes. Factors associated with this phenomenon included a higher IOP and longer SO tamponade duration. © The Author(s) 2017.

Background Intravitreal injection (IVI) is a very common vitreoretinal procedure, and multiple injections are often required per patient. This systematic review was conducted to evaluate the effectiveness of various local anesthetic techniques in reducing pain during injection. Methods A systematic review was conducted based on searches of Cochrane, LILACS, PubMed, Scopus, Web of Science, and the gray literature (Google Scholar). The end search date was February 19, 2016, across all databases. We classified pain by converting visual analog scale (VAS) scores (0–100 mm) into Jensen’s classification levels: 0–4, no pain; 5–44, mild pain; 45–74, moderate pain; and 75–100, severe pain. An intervention was considered clinically significant when pain score change was >12 mm on a 100-mm scale. Results Eight studies out of 23 met the eligibility criteria. The total number of patients was 847. Most studies (5/8 [62.5%]) were at unclear risk of bias because of unclear randomization, thus providing only moderate evidence to this review. The anesthetic techniques included eye drops with proparacaine, tetracaine or cocaine, a lidocaine pledget or gel, and subconjunctival injection of 2% lidocaine or 0.75% levobupivacaine. No study comprised all of the techniques. Pain was mild (VAS scores, 5–44 mm) regardless of anesthetic technique. A clinically significant intervention (pain score change >12 mm) was found for only one study comparing proparacaine drops, lidocaine gel, and subconjunctival lidocaine; in that study, a subconjunctival injection of 2% lidocaine provided the greatest pain reduction. A meta-analysis was not possible due to study heterogeneity. Conclusions Patient pain during IVI under topical anesthesia is mild regardless of anesthetic technique. A subconjunctival injection of 2% lidocaine could be an option for highly sensitive patients. However, with moderate level of evidence, no single anesthetic technique could be defined as the best option for IVI. Electronic supplementary material The online version of this article (doi:10.1186/s40942-017-0076-9) contains supplementary material, which is available to authorized users.

BACKGROUND AND OBJECTIVE: To study the safety and efficacy of intravitreal injections of ziv-aflibercept (IVI-ZA) (Zaltrap; Sanofi-Aventis and Regeneron Pharmaceuticals, Tarrytown, NY) during a period of 48 weeks in patients with diabetic macular edema (DME). PATIENTS AND METHODS: Seven consecutive patients with DME were enrolled and submitted to 12 consecutive IVI-ZA with a 4-week interval. The safety parameters included changes in full-field electroretinogram (ERG) and systemic or ocular complications, and the efficacy parameters were the mean change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: No significant differences were found in any ERG component after IVI-ZA, and no systemic or ocular complication was observed. The improvement of BCVA was most significant after the first IVI-ZA and remained until week 48 ( P < .05). The CRT significantly decreased during the course of 48 weeks. CONCLUSION: The 48-week results are consistent with our previous 24-week findings, supporting IVI-ZA as a safe, efficient, and well-tolerated therapy for patients with DME. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:245–250.]

Intravitreal injection (IVT) is one of the most common vitreoretinal procedures, a large majority are performed with local anesthesia. The purpose of this study was to investigate the safety to the cornea and anesthetic efficacy of five concentrations of lidocaine gel.A prospective clinical trial was conducted testing lidocaine gel in five preparations: 2, 3.5, 5, 8 and 12%. Patients with macular degeneration, diabetic edema or retina vein occlusion were scheduled for intravitreal treatment received topical anesthesia with lidocaine gel 5 and 10 min before the procedure. Patients answered the visual analog scale for pain during the procedure. Corneal and conjunctival was evaluated using the Oxford scale.In total, 260 patients were randomized into five groups. The mean pain scores (± standard deviation) were 2.63 (± 1.68) in the 2% group, 2.08 (± 1.35) in the 3.5%; 2.00 (± 1.65) in the 5%, 1.93 (± 1.40) in the 8% and 1.83 (± 1.35) in the 12% group. Mean pain score among all groups was similar (p = 0.077). There was no significant difference between groups in regard to keratitis mean score (p = 0.897).Lidocaine gel at concentrations from 2 to 12% induced similar anesthetic effect for IVTs, without adverse effects on cornea and conjunctiva.

The aim of this study is to analyze the agreement between the classifications based on morphology and diameter of vitreomacular traction (VMT) syndrome, as well as to correlate the morphological findings of VMT with specific maculopathies. Fifty-three eyes with VMT syndrome were categorized into two classifications based on optical coherence tomography images: the VMT morphology (V- or J-shaped) and the diameter of adhesion (focal≤1500 μm or broad>1500 μm). High correlation was seen between V-shaped and focal-VMT and between J-shaped and broad-VMT (kappa=0.850; P

To investigate the relationship between retinal sensitivity and persistence of subretinal fluid and then to analyze microperimetry as a prognostic predictor of acute central serous chorioretinopathy.A prospective observational study. Fourteen eyes of 14 patients presenting with first episode acute central serous chorioretinopathy were enrolled and underwent ocular examination, spectral domain optical coherence tomography, and MAIA microperimetry were performed. After three months of follow-up, without any treatment, visual acuity and spectral domain optical coherence tomography macular thickness assessments and microperimetry were repeated. The main outcome was to find a relation between initial macular sensitivity and persistence of subretinal fluid. A receiver operating characteristic curve was plotted to indicate the best macular sensitivity cutoff point that would be able to predict whether a patient with acute central serous chorioretinopathy would progress to the chronic form. According to the cutoff, we calculated the sensitivity, specificity, and positive and negative predictive values for macular sensitivity as a method to predict persistence of subretinal fluid.On the basis of the receiver operating characteristic curve, a cutoff of 20 dB macular sensitivity was obtained, as the best balance between sensitivity and specificity to predict chronicity. Using this cutoff, the method had a sensitivity of 71% and specificity of 100% with a positive predictive value of 100% and negative predictive value of 78%. Furthermore, it was found that eyes with acute central serous chorioretinopathy and microperimetry of less than 20 dB had a relative risk of 4.5 to develop subretinal fluid persistence.Microperimetry with a cutoff of 20 dB may be a useful test to predict the persistence of subretinal fluid, allowing the ophthalmologist to use treatment tools earlier, preventing extracellular damage and visual impairment.

Vital dyes have advanced diagnosis and surgical technique in various specialties, including oncology, gastroenterology and ophthalmology. Intra-operative and diagnostic dyes are finding uses in all areas of ophthalmology, including cornea, cataract, retina, glaucoma, orbit and conjunctiva. We provide a summary of current knowledge of the chemical concepts of vital dyes in ophthalmology. 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.

We retrospectively evaluated a heavy silicone oil (HSO) as a long-term intraocular endotamponade agent to treat complicated RD by inferior PVR in 25 eyes of 25 patients. Patients underwent PPV and injection of Oxane HD as an internal tamponade agent. A comparison of preoperative and postoperative BCVA at month 1, month 6, and last visit was made in the group in which HSO was removed and in the group in which HSO was not removed. Statistical calculations were performed using the Wilcoxon test. The HSO was removed from 11 patients after a mean of 26.55 ± 21.38 months. The HSO remained inside the vitreous cavity in 14 eyes due to a high chance of PVR recurrence (mean follow-up period, 11.07 ± 7.44 months). Anatomic success was achieved in 92%. The BCVA in the group, in which HSO was not removed, improved significantly during the first 6 months. Among the patients who had the oil removed, there was improvement in BCVA after 1 month. Oil emulsification was the most common adverse effect in 52% of eyes. HSO is an effective tamponade in complex rhegmatogenous and tractional RD complicated by PVR. HSO can remain in the eye for long periods with relative tolerability and safety.

Fifteen patients with exudative age-related macular degeneration were treated with intravitreal injections of ziv-aflibercept (1.25 mg). Ziv-aflibercept improved the best-corrected visual acuity, multifocal electroretinography amplitudes, and central retinal thickness from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period., Purpose: To evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration. Methods: Fifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment. Results: Between baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P < 0.0001) from 9.51 ± 1.36 mm3 to 8.08 ± 1.34 mm3, and the a-wave implicit time increased, with no differences in the other full-field electroretinography parameters. The average multifocal electroretinography macular responses within the first central 15° showed significantly (P < 0.05) increased P1 amplitudes at 26 weeks. No systemic or ocular complications developed. Conclusion: Intravitreal ziv-aflibercept significantly improved the best-corrected visual acuity, multifocal electroretinography amplitudes, central retinal thickness, and total macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.

The goals of this study were to determine the potential for use of the natural anthocyanins from the açai fruit (Euterpe oleracea) during vitreoretinal surgery and the ideal physicochemical properties of the dye.We evaluated the color variations of the dye at different pHs and osmolarities with or without the use of mordants as a potential new tool for internal limiting membrane peeling. The extracts of anthocyanin from the açai fruit were analyzed by spectrophotometry to determine the degree of color variations associated with various pHs and osmolarities. The experiments were conducted in test tubes filled with tryptophan soya media and Petri dishes prepared with agar media.We observed various shades of green, red, and purple in the extracts of the anthocyanin dye at different pHs and osmolarities. The assay to adjust the anthocyanin solution similar to the physiologic retinal environment (osmolarity, 300 mOsm; pH, 7.00) resulted in a shade of purple that may be useful to stain the intraocular microstructures during vitreoretinal surgery. The physicochemical property of the purple anthocyanin solutions from the açai fruit was observed at physiologic pH and osmolarity.Anthocyanins from the açai fruit may be useful to enhance visualization of the intraocular microstructures during vitreoretinal surgery.

PURPOSE To evaluate drusenoid retinal pigment epithelial detachments (DPED) secondary to age-related macular degeneration (AMD) using spectral-domain optical coherence tomography imaging. METHODS In this prospective natural history study, eyes from patients with the diagnosis of nonexudative AMD and DPEDs were followed for at least 6 months. Eyes were scanned using the Cirrus spectral-domain optical coherence tomography instrument and the 200 × 200 A-scan raster pattern. A custom software was used to quantify volumetric changes in DPEDs and to detect the evolution and formation of geographic atrophy and choroidal neovascularization. Changes in DPED area and volume and development of the advanced forms of AMD were the main outcome. RESULTS Of the 130 patients (186 eyes) with nonadvanced AMD, 11 patients (16 eyes) presented with DPEDs during the study. Mean follow-up was 18.5 months. Most DPEDs had an area exceeding 1 disk area (14 of 16 eyes) based on color fundus images with a mean area of 4.19 mm(2) (SD = 1.35) measured by spectral-domain optical coherence tomography. The mean volume at the time the DPED was diagnosed was 0.48 mm(3) (SD = 0.28). Four different patterns of progression were observed: DPEDs remained unchanged in 8 of 16 eyes (50%), DPEDs tended to increase in volume before progressing to geographic atrophy in 5 eyes (31.25%) and choroidal neovascularization in 2 eyes (12.5%), and a DPED decreased by more than 50% without progressing to geographic atrophy or choroidal neovascularization in 1 eye (6.25%). CONCLUSION Spectral-domain optical coherence tomography imaging is able to detect subtle changes in the area and volume of DPEDs. Quantitative spectral-domain optical coherence tomography imaging of DPEDs is useful for identifying the natural history of disease progression and as a clinical tool for monitoring eyes with AMD in clinical trials.

Purpose: To investigate the in vitro effect of vital dyes on toxicity and apoptosis in a human retinal pigment epithelial cell line. Methods: ARPE-19 cells were exposed to brilliant blue (BBG), Evans Blue (EB), bromophenol blue (BroB), indocyanine green (ICG), infracyanine green (IfCG), light green (LG), fast green (FG), indigo carmine (IC) and Congo red (CR). Balanced salt solution was used as the control. Five different concentrations and 2 exposure times were tested. Cell viability was determined by the MTS (1-solution methyl thiazolyl tetrazolium) assay and apoptosis by Bax expression on Western blot. Results: All dyes significantly reduced cell viability after 3 min of exposure at all concentrations (p < 0.01), except for BBG that was safe at concentrations up to 0.25 mg/ml and CR up to 0.05 mg/ml, while LG was safe at all concentrations. Toxicity was higher after 30 min of exposure. Expression of Bax was upregulated after all dye exposures, except BBG; ICG had the highest Bax expression (p < 0.01). Conclusions: Overall the safest dye was BBG followed by LG, IfCG, FG, CR, IC, BroB, EB and ICG. ICG was toxic at all concentrations and exposure times tested. Moreover, BBG was the only dye that did not induce apoptosis in ARPE-19 cells.

The purpose of this study was to determine whether natural dyes facilitate posterior hyaloid detachment (posterior vitreous detachment [PVD]) and retinal internal limiting membrane (ILM) peeling in human eyes.Open-sky vitrectomy with posterior hyaloid and ILM removal was performed in 86 human cadaveric eyes. After core vitrectomy, 11 different dyes were injected into the vitreous cavity to aid hyaloid detachment and ILM removal. The dyes were allowed to settle on the macula for 5 minutes after PVD and were removed by mechanical aspiration. Intraocular forceps were used for ILM peeling, which was confirmed by light microscopy of the peeled tissue. Acai fruit (Euterpe oleracea) extract and 10 additional dyes from plants or animal sources were tested: pomegranate (Punica granatum), logwood (Haematoxylum campechianum), chlorophyll extract from alfalfa (Medicago sativa), cochineal (Dactylopius coccus), hibiscus (Hibiscus rosa-sinensis), indigo (Indigofera tinctoria), paprika (Capiscum annuum), turmeric (Curcuma longa), old fustic (Maclura tinctoria), and grape (Vitis vinifera).The dyes facilitated PVD and ILM peeling. Acai fruit (E. oleracea) extract, logwood (H. campechianum), cochineal (D. coccus), and old fustic (M. tinctoria) facilitated PVD in all cases; dye-assisted PVD was compared with triamcinolone-assisted PVD performed previously in a comparative model. Acai fruit (E. oleracea) extract, cochineal (D. coccus), and chlorophyll extract from alfalfa (M. sativa) showed the best capability for ILM staining; dye-assisted ILM removal was compared with the ILM peeling guided by indocyanine green staining performed previously in a comparative model. Light microscopy confirmed the ILM removal in all cases.Anthocyanin dye of the acai fruit (E. oleracea) and the dyes from cochineal (D. coccus) and chlorophyll extract from alfalfa (M. sativa) resulted in the best capability for posterior hyaloid and ILM staining in human cadaveric eyes and may be a useful tool for vitreoretinal surgery.

Purpose: Intravitreous injection of vital dyes, e.g. brilliant blue (BBG), promotes better visualization of the internal limiting membrane (ILM). This paper investigates the staining properties of BBG depending on different incubation times and 2 types of solvents - 5% glucose (GL) or saline solution - in a prospective study in patients. Methods: This paper investigates various aspects of BBG in various methods. An interventional prospective study was conducted in patients to examine the binding properties of the blue dye diluted in either saline or 5% GL to epiretinal membranes (ERMs) and ILMs. Forty-nine consecutive patients older than 18 years scheduled for macular ERM, vitreomacular traction and macular hole surgeries were prospectively recruited. The primary outcomes of this study were the degree of ILM and ERM staining. The secondary outcomes of the study were the need of reinjection of BBG or any other dye, the ability of BBG to stain the vitreous, and frequency of complications. The staining of the ILM and ERM were graded as no staining, little, moderate or strong staining. Results: There was no correlation between age (p = 0.32) or gender (p = 0.33) in the staining affinity of BBG to either the ILM or ERM. BBG may be an appropriate staining agent for the ILM in the majority (82%) of surgeries; however, in approximately half of the cases (45%) surgeons considered BBG not enough for ERM coloring and visualization. There is a tendency of BBG to stain the ILM better when saline solution is used compared to GL 5%; however, this was not statistically significant (p = 0.64). There was no difference in the staining efficacy of BBG to the ERMs by either solution (p = 0.70), despite the low staining affinity. Conclusion: BBG became the state-of-the-art dye for ILM identification. Differences in staining properties may imply that BBG should not be considered as first-line stain for ERM surgery. BBG is effective in ILM staining in over 80% of macular hole surgeries.

Background: Retrospective review of one acute syphilitic posterior placoid chorioretinitis (ASPPC) case with serological evidence of syphilis who had ocular signs and symptoms not attributable to other diseases. Enface and spectral-domain optical coherence tomographySD-OCT were analyzed at the time of presentation and at 1-month visit following initiation of treatment. The study patient underwent standard treatment for neurosyphilis. Results: Ophthalmic examination and imaging studies were consistent with the diagnosis of ASPPC. The patient age was 33 year-old and the baseline visual acuity was 20/400 and 20/80 in the right and left eyes, respectively. At presentation, SD-OCT scans showed disruption and loss of the ellipsoid zone (EZ), small nodular elevations on retinal pigment epithelium (RPE) and punctate hyperreflectivity in the choroid. Enface OCT at the level of RPE and EZ demonstrated multiple hyperreflective dot-like lesions simmetrically distributed within the macular area. These dot-like lesions corresponded to the small nodular elevations on RPE and to disruption/loss of EZ observed with SD-OCT. One month after neurosyphilis therapy, the visual acuity improved and the outer retinal changes partially reversed in both eyes. Conclusions: We report the outer retinal findings and its correlation using both en-face and SD-OCT in a patient with ASPPC. En-face OCT imaging provides a more precise outer retinal layers analyses allowing a better understanding of the ASPPC pathophysiology. Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil Fed Univ Sao Paulo UNIFESP, Rua Botucatu,821,Vila Clementino, BR-04023062 Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil Fed Univ Sao Paulo UNIFESP, Rua Botucatu,821,Vila Clementino, BR-04023062 Sao Paulo, SP, Brazil Web of Science

Lutein and zeaxanthin, two carotenoid pigments of the xanthophyll subclass, are present in high concentrations in the retina, especially in the macula. They work as a filter protecting the macula from blue light and also as a resident antioxidant and free radical scavenger to reduce oxidative stress-induced damage. Many observational and interventional studies have suggested that lutein and zeaxanthin may reduce the risk of various eye diseases, especially late forms of AMD. In vitro and in vivo studies indicate that they could protect various ocular cells against oxidative damage. Recent research has shown that in addition to traditional mechanisms, lutein and zeaxanthin can influence the viability and function of cells through various signal pathways or transcription factors: for instance, they can affect immune responses and inflammation, and have anti-angiogenic and anti-tumor properties. This review covers the basic aspects and results of recent studies regarding the effects of lutein, zeaxanthin and other carotenoids, such as meso-zeaxanthin, on the eye in different clinical and experimental models and the management of various ocular diseases using these molecules.

In the last few years, monoclonal antibodies have revolutionized the treatment of retinal neovascular diseases. More recently, a different class of drugs, fusion proteins, has provided an alternative treatment strategy with pharmacological differences. In addition to commercially available aflibercept, two other drugs, ziv-aflibercept and conbercept, have been studied in antiangiogenic treatment of ocular diseases. In this scenario, a critical review of the currently available data regarding fusion proteins in ophthalmic diseases may be a timely and important contribution. Aflibercept, previously known as VEGF Trap Eye, is a fusion protein of VEGF receptors 1 and 2 and a treatment for several retinal diseases related to angiogenesis. It has firmly joined ranibizumab and bevacizumab as an important therapeutic option in the management of neovascular AMD-, DME- and RVO-associated macular edema. Ziv-aflibercept, a systemic chemotherapeutic agent approved for the treatment of metastatic colorectal cancer, has recently drawn attention because of its potential for intravitreal administration, since it was not associated with ERG-related signs of toxicity in an experimental study and in human case reports. Conbercept is a soluble receptor decoy that blocks all isoforms of VEGF-A, VEGF-B, VEGF-C, and PlGF, which has a high binding affinity for VEGF and a long half-life in vitreous. It has been studied in a phase three clinical trial and has shown efficacy and safety. This review discusses three fusion proteins that have been studied in ophthalmology, aflibercept, ziv-aflibercept and conbercept, with emphasis on their clinical application for the treatment of retinal diseases.

To compare same-day pain control and safety of 2 different anesthetic gels utilizing 5% and 2% lidocaine gel. Main outcome is to determine whether 5% lidocaine gel is more effective in decreasing pain during conjunctival clamping compared to 2% lidocaine gel 5 and 10 min after gel application.This is a prospective, randomized double-blind clinical trial. Patients were randomized to receive 2% or 5% lidocaine gel in each eye. Discomfort during the gel instillation and pain during conjunctival clamping 5 and 10 min after gel application were compared. Extent of corneal conjunctival staining was graded according to the Oxford scale.Eighty eyes of 40 patients were enrolled. The groups were similar in gender, with a mean age of 48 ± 16.26 years. The 5% lidocaine gel resulted in higher discomfort during initial instillation (P = 0.092), however, the pain during conjunctival clamping was lower in the 5% lidocaine gel eyes (P = 0.564) in both 5 and 10 min later (P 0.001). The majority of patients (80%) had no corneal conjunctival dye staining. The tear break-up time was not statistically different after lidocaine gel 2% (20.35 ± 7.37 s) and lidocaine 5% (19.75 ± 7.00 s).Five percent and 2% lidocaine gel have similar efficacy controlling pain 5 min after instillation, however, 5% lidocaine gel appears to be more effective with a longer duration of action, without corneal toxicity. There was no corneal toxicity noted with either concentration.

Purpose.To evaluate daily spectral-domain optical coherence tomography (SD-OCT) changes in naive-treatment patients with diagnosis of exudative age-related macular degeneration (AMD) treated with intravitreous bevacizumab (1.25 mg), during a 30-day follow-up period.Methods.In prospective, interventional study, SD-OCT was performed daily for 30 days after the first intravitreal injection. The baseline, initial-decrease, minimal, and final central retinal thicknesses (CRTs) were assessed.Results.Nine eyes of nine patients with neovascular AMD were enrolled. The mean baseline CRT was625.3±182.5 μm, and the mean final CRT was383.4±163.0 μm (mean difference,206.1±167.6 μm), a difference that reached significance (P=0.006). After the first injection, the initial decrease in the CRT was seen as an average of one day after injection (mean CRT,503.6±189.10 μm;P=0.0431). The speed of the reduction in the CRT tended to decrease by day 17. The mean CRT was336.5±105.44 μm and the mean minimal CRT on day 30 was320.75±96.38 μm.Conclusion.The CRT decreased early after the first injection. We observed a tendency for reductions in the speed with which the CRT decreased by day 17 after the first injection, which may affect retreatment regime.