INTRAVITREAL DEXAMETHASONE IMPLANT MIGRATION INTO THE ANTERIOR CHAMBER: A Multicenter Study From the Pan-American Collaborative Retina Study Group.

PURPOSE: To establish the prevalence and risk factors for intravitreal dexamethasone implant migration into the anterior chamber in eyes with macular edema. METHODS: This was a multicenter, retrospective, observational chart review of data that included patients with macular edema who had been treated with at least one intravitreal dexamethasone injection. Patients with incomplete chart information during the follow-up period were excluded. RESULTS: The prevalence of implant migration in 468 patients, considering the number of injections, was 1.6%, with significant associations between implant migration and cataract surgery (P = 0.043) and intraocular lens status (P = 0.005) and a trend toward statistical significance (P = 0.057) with vitrectomy. A higher rate of implant migration into the anterior chamber was observed in vitrectomized eyes (4.8%) when compared with patients who did not undergo a vitrectomy (1.6%). The implants that migrated were removed with forceps with/without viscoelastic expression or with 20-gauge cannulas connected to the vitreous cutter machine. CONCLUSION: The risk of implant migration into the anterior chamber was 1.6%. Risk factors were a history of cataract surgery or vitrectomy and aphakia. When anterior migration occurs, rapid removal is advised, especially if corneal edema is present.

An experimental and clinical study on the initial experiences of Brazilian vitreoretinal surgeons with heads-up surgery.

PURPOSE: To evaluate the initial experiences of several vitreoretinal surgeons in Brazil, both experienced and beginners, with a three-dimensional (3D) system, and to report the advantages and disadvantages of this technology. We also report surgical manipulations performed using the heads-up method in porcine eyes. For full-thickness idiopathic macular holes (MHs), we analyzed the times required for pars plana vitrectomy (PPV) and internal limiting membrane (ILM) rhexis by using traditional microscopy and 3D system, and to evaluate anatomical surgical results. METHODS: During experimental vitreoretinal surgery on porcine eyes, two retinal surgeons applied the heads-up method. In clinical surgery, 14 retinal surgeons performed almost all types of vitreoretinal surgeries in association with facectomy, Ahmed glaucoma valve implant, or minimally invasive glaucoma surgery using an iStent®. The Ngenuity® 3D Visualization System was digitally integrated with intraoperative optical coherence tomography, the Verion™ Image-Guided System, and an endoscope (with a modified GoPro® camera). To compare the 3D system with traditional microscopy, ergonomics, educational value, image sharpness, depth perception, field of view, advantages and disadvantages, and technical feasibility were assessed using a questionnaire. One year later, the 14 surgeons answered the same questionnaire again, in order to assess whether they became more comfortable or not with 3D. For treating MHs, four surgeons (surgeon 1, fellows 1, 2, 3) performed the total of 40 surgeries. Each one performed 10 surgeries (5 with traditional microscopy and 5 with 3D visualization). The completion time for PPV and ILM rhexis were determined by using both methods. RESULTS: In porcine eyes, disabling the color channels allowed better visualization of the ILM, either with Brilliant Blue G (BBG), indocyanine green chorioangiography (ICG), or açai dye; transillumination through the sclera was also better without a color channel, but visualization of the peripheral vitreous was better with a blue channel. Regarding clinical experience, the questionnaire responses showed that the respondents generally favored the heads-up method compared with traditional microscopy (p < 0.05); however, despite a slightly higher average score, the 3D system was not statistically significantly preferred in terms of technical feasibility (p = 0.1814). Answering again the same questionnaire 1 year later, the 14 surgeons felt more comfortable with 3D (p < 0.05). The type of surgery benefitting most from the 3D system was peeling of the ILM or epiretinal membrane (p < 0.001), and that receiving the least benefit was anterior segment surgery (p < 0.001). In addition, surgeons did not report benefits of color channels, preferring to disable it (p < 0.001). 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 3D surgery for each surgeon. Surgeon 1 had always been faster than his fellows. Thirty-six (90%) full-thickness MHs were successfully closed with one surgery. CONCLUSIONS: The 3D system was preferred to traditional microscopy. The 3D system was especially helpful for certain specific types of surgeries and served as an educational tool, having reduced illumination and allowing precise focusing. Concerning MH surgery, heads-up method was similar to traditional microscopy regarding length of time and anatomical surgical results. As a digital platform, it will be amenable to constant upgrades and may ultimately become the new standard for ophthalmic surgery.

A new dye based on anthocyanins from the acai fruit (Euterpe oleracea) for chromovitrectomy in humans: clinical trial results.

PURPOSE: 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). METHODS: 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. RESULTS: The posterior hyaloids and ILMs stained purple in all eyes. The final best-corrected visual acuity improved significantly (p < 0.001) from preoperatively (1.37 ± 0.29) to 180 days postoperatively (1.05 ± 0.43). The MHs closed in 76% of eyes. CONCLUSION: The acai dye at a 25% concentration identified posterior hyaloids and ILMs during PPVs in humans. Dye toxicity was unlikely.

Comparison of 577-nm Multispot and Standard Single-Spot Photocoagulation for Diabetic Retinopathy.

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.

Learning curve of three-dimensional heads-up vitreoretinal surgery for treating macular holes: a prospective study.

PURPOSES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

CLINICAL AND ELECTROPHYSIOLOGICAL EVALUATION AFTER INTRAVITREAL ZIV-AFLIBERCEPT FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

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 mm to 8.08 ± 1.34 mm, 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.

INTRAVITREAL INJECTIONS OF ZIV-AFLIBERCEPT FOR DIABETIC MACULAR EDEMA: A Pilot Study.

PURPOSE: 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. METHODS: 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. RESULTS: 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 (P < 0.05). The central retinal thickness significantly decreased during the course of 24 weeks. CONCLUSION: Intravitreal injections of ziv-aflibercept seem to be a safe and effective treatment option for diabetic macular edema.

Viability of Primary Human Pigment Epithelium Cells and Muller-Glia Cells after Intravitreal Ziv-Aflibercept and Aflibercept.

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.

Effect of lens status in the surgical success of 23-gauge primary vitrectomy for the management of rhegmatogenous retinal detachment: the Pan American Collaborative Retina Study (PACORES) group results.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Potential Risk Factors for Ocular Pain in Patients Undergoing Multiple Intravitreal Injections of Anti-Vascular Endothelial Growth Factor.

Purpose: To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may influence pain sensitivity. Methodology: This is a prospective, observational, case series study involving patients who underwent multiple (≥3) pro re nata intravitreal injections of ranibizumab or aflibercept to treat any cause of chorioretinal vascular disease. Ocular pain was assessed by the numerical analog scale during intravitreal injection. For this study, the main variable was ocular pain and the secondary variables included age, sex, previous history of glaucoma, primary retinal vascular disease, severe dry eye history, trigeminal pain, scleral buckle surgery, collagen diseases, fibromyalgia, severe migraine history, pars plana vitrectomy, scleral thickness measurements, and type of anti-VEGF. Results: In a total of 894 patients, 948 eyes (4822 intravitreal injections), 793 patients (88.6%) had ocular pain sensitivity between no pain to mild pain, 80 patients (8.9%) had moderate ocular pain, 15 patients (1.6%) had severe ocular pain, and 6 patients (0.7%) had extremely severe ocular pain. Patients with severe dry eye (p = 0.01) and previous history of scleral buckle surgery (p = 0.01) showed a significant correlation with ocular pain during intravitreal injection. Pars plana scleral thickness (>550 um) and diabetic neuropathy were associated with ocular pain but did not meet the criteria for statistical significance (p = 0.09 and p = 0.06, respectively). Conclusion: Dry eye and prior scleral buckle surgery may contribute to pain associated with intravitreal injection. These issues should be taken into consideration in patients undergoing multiple intravitreal injections.

Investigation of the retinal biocompatibility of acid violet for chromovitrectomy.

PURPOSE: The primary objective was to investigate the retinal biocompatibility of acid violet (AV) as a vital dye for chromovitrectomy. The secondary objective was to evaluate the capacity of AV to stain the anterior capsule of the lens. METHODS: An amount of 0.05 ml of 0.25 g/l and 0.5 g/l AV was injected intravitreally in the OD, while balanced salt solution (BSS) was applied in the OS for control. Clinical examination and histology with light microscopy (LM) were performed after 7 days. Retinal cell layers were evaluated for morphologic alterations and number of cells. The electroretinographic (ERG) changes were assessed at baseline and 7 days. In another part of the study, 0.1 ml of 0.25 g/l AV was injected into the anterior chamber of ex-vivo porcine eyes, and its capacity to stain the anterior capsule was determined. Cadaveric eyes were used to test the capacity of AV to stain the internal limitant membrane (ILM) during vitrectomy. RESULTS: The gross histopathologic appearance of the retina, choroids, sclera, and optic nerve was within normal limits, without any signs of severe retinal necrosis or cystic degeneration. AV caused no substantial retinal alterations in retinal layers by LM at either the lower or higher dose when compared with the control eye. The injection of AV did not induce considerable ERG alterations. The violet dye stained the anterior capsule after anterior chamber injection and the ILM, allowing a safer capsulorrhexis and vitrectomy. CONCLUSION: Acid violet may be safe for the retina at concentrations of 0.25 and 0.50 g/l after intravitreous injection, and may be used as a vital dye for staining the anterior capsule and the ILM.

Posterior hyaloid detachment and internal limiting membrane peeling assisted by anthocyanins from acai fruit (Euterpe oleracea) and 10 other natural vital dyes: experimental study in cadaveric eyes.

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Effect of vital dyes on retinal pigmented epithelial cell viability and apoptosis: implications for chromovitrectomy.

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.

Biochemical analysis and decomposition products of indocyanine green in relation to solvents, dye concentrations and laser exposure.

PURPOSE: To investigate pH, ions, osmolarity and precipitation of indocyanine green (ICG), as well as the profile of ICG decomposition products (DPs) after laser exposure and the interaction with quenchers. METHODS: ICG was diluted in water, 5% glucose (GL) or balanced salt solution (BSS) to achieve concentrations of 2.5, 1, 0.25 and 0.1 mg/ml. Osmolarity, pH and precipitation were analyzed immediately and after 24 h. Precipitation analyses were done with a scanning electron microscope. Anion and iodate analyses of ICG and infracyanine green (IfCG) were performed by capillary zone electrophoresis. With regard to DPs, 0.5 mg/ml of ICG was assessed with high-performance liquid chromatography (HPLC) after 810-nm laser irradiation. DP profiles were evaluated with ICG dilution in quenchers (Trolox, histidine and DABCO) in 3 concentrations (0.1, 1 and 10 M). RESULTS: BSS promoted iso-osmotic ICG solutions of 208 mOsm (147-266) compared to GL with 177 mOsm. BSS solutions had a higher physiological pH of 7.2 compared with the GL one of 6.55. ICG precipitated more when diluted with BSS (5.95 mg); in contrast, GL showed less precipitate (3.6 mg). IfCG has no iodine derivates and other ICGs have an average 4.6% of iodate derivates. From HPLC analysis, 5 DPs were observed. The rate of DPs was higher when BSS was used (p < 0.05). Five DPs have been generated with ICG, and they may be altered with the quenchers DABCO, histidine and Trolox. CONCLUSIONS: BSS dilution induces more precipitation and DPs. ICG dilution in any solvent induces DPs. Quencher use reduces the amount of toxic DPs.

Retinal microvascular density modifications during the water drinking test.

PURPOSE: The water drinking test (WDT) is a well-known stress test that increases intraocular pressure (IOP) momentarily and can indicate risk of glaucoma progression. This study focuses on correlating changes in the retinal microvascular plexus with the WDT in young healthy subjects. METHODS: A total of 20 eyes of 20 healthy young subjects (mean age 24.37 ± 2.17 years) were included in this study. In our protocol, WDT consisted of drinking 1 L of water within 5 min. Outcome measures in this prospective observational study were mean arterial pressure (MAP), heart rate (HR), IOP, and retinal vessel density of both superficial and deep macular retina using optical coherence tomography angiography (OCTA), which were assessed before water ingestion and four times after at 15-min intervals. OCTA images were later quantified by fractal analysis (box counting [Dbox]). One-way repeated measures analysis of variance (ANOVA) was used to assess the effects of WDT on each of the parameters. RESULTS: The WDT resulted in significant peak changes of the following parameters compared to baseline: IOP: 15.63 ± 3.37 versus 18.38 ± 4.53 mmHg at 30 min, p < 0.001; HR: 75.74 ± 12.23 versus 64.95 ± 11.37 bpm at 15 min, p < 0.001; deep retinal vessel density 1.758 ± 0.14 versus 1.749 ± 0.16 at 15 min, p = 0.040. CONCLUSIONS: Besides IOP elevation and systemic effects in HR, WDT is associated with temporary modifications of the deep vascular plexus in young healthy subjects.

Quantitative assessment of silicone oil release with siliconized and silicone oil-free syringes by microflow imaging microscopy.

PURPOSE: Since particles are released in syringes during intravitreal injections, we assessed them quantitatively after agitating syringes commonly used for intravitreal injections. METHODS: With and without agitation, the SR 1-ml insulin, Becton-Dickinson Ultra-Fine 0.3-ml Short Needle with a half-unit scale, HSW Norm-Ject Tuberculin, and Becton-Di-ckinson 1-ml Luer Lok Tip were examined with buffer and bevacizumab, aflibercept, and ziv-aflibercept. Flow imaging microscopy was performed to assess the particle numbers, concentrations, morphology, and size distribution. RESULTS: Using the Becton-Dickinson Ultra-Fine syringe, the average particle count after agitation was higher than in the no-agitation group. For particles greater than 10 and 25 µm, differences were observed using the SR syringe between the two studied conditions. There were no significant differences in the means for the other syringes. Without agitation, the SR syringe had the highest number of particles (2,417,361.7 ± 3,421,575.5) followed by the Becton-Dickinson Ultra-Fine with 812.530,9 ± 996.187,2. The Becton-Dickinson Luer Lok Tip and HSW Norm-Ject performed equally with 398,396.8 ± 484,239.2 and 416,016.4 ± 242,650.1 particles, respectively. CONCLUSIONS: Flicking syringes to eliminate air bubbles results in increased numbers of particles released during intravitreal injections into the human vitreous.

Ocular inflammation after agitation of siliconized and silicone oil-free syringes: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Noninfectious endophthalmitis may be misdiagnosed, leading to serious clinical implications. So far, its causative factors remain unknown. Therefore, this study assessed the role of silicone oil and syringe agitation in the development of inflammation after intravitreal injection of aflibercept. METHODS: A randomized, double-blind, controlled clinical trial included subjects with an indication of intravitreal antiangiogenic therapy prior to vitrectomy for proliferative diabetic retinopathy. Aflibercept was injected 48 h before surgery. The control group received the injection without agitation, while the intervention group was injected with a previously agitated syringe by flicking with either a siliconized or silicone oil-free syringe. The primary endpoint was the presence of anterior chamber reaction (ACR) at 48 h. Aqueous samples were collected and underwent cytometric bead array analysis for quantification of interleukins and chemokines. RESULTS: Forty-one individuals were included (21 in the agitation group and 20 in the no-agitation group). None of the included eyes showed baseline signs of AC cells, hyperemia or pain complaint, while 10% of control group and 80% of agitation group showed AC cells 48 h after injection of aflibercept with SR syringe. There were no differences in the mean variations of all cytokines and chemokines by agitation status. However, there was a marginally significant increase between the mean variations of IP-10 (p = 0.057) and IL-8 (p = 0.058) in the siliconized one. CONCLUSION: This clinical trial discloses a potential role of agitation and siliconized syringes in the development of inflammation after an intravitreal injection of aflibercept. These findings have important clinical implications for all healthcare practitioners who perform intravitreal injections. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials, RBR-95ddhp. Registered 12 May 2019, http://www.ensaiosclinicos.gov.br/rg/RBR-95ddhp/.

Comparison of 20-, 23-, and 25-gauge air infusion forces.

PURPOSE: To determine and compare 20-, 23-, and 25-gauge retinal infusion air jet impact pressure (force per unit area) in an experimental setting. METHODS: Experimental laboratory investigation. Infusion cannulas were connected to a compressed air system. A controlled valve mechanism was used to obtain increasing levels of infusion pressure. Each infusion tube was positioned in front of a manual transducer to measure force. Impact pressure was calculated using known formulas in fluid dynamics. RESULTS: The 20-gauge infusion jet showed similar impact pressure values compared with the 23-gauge infusion jet. Both showed higher levels than the 25-gauge infusion jet. This was because of the smaller jet force for the 25-gauge system. CONCLUSION: In this experimental study, both the 23- and the 20-gauge air infusion jet showed higher impact pressure values compared with the 25-gauge air infusion jet. This could be of concern regarding air infusion during 23-gauge vitrectomy since retinal damage has been shown in standard-gauge surgeries.

Heads-up Digitally Assisted Surgical Viewing with Intraoperative Optical Coherence Tomography for Myopic Schisis Repair.

PURPOSE: To describe the surgical approach with a screen-based heads-up, three-dimensional (3-D) digital viewing with intraoperative optical coherence tomography (I-OCT) for the successful repair of a myopic macular schisis (MMS) case. CASE REPORT: A 62-year-old woman with vision loss in the left eye was scheduled for pars plana vitrectomy (PPV) and MMS repair. Surgery was performed using the NGENUITYⓇ system for surgical viewing, and foveal-sparing internal limiting membrane (fs-ILM) peeling was performed without gas tamponade, after confirming the absence of iatrogenic macular hole with I-OCT. There were no intraoperative or postoperative complications. Visual acuity improved to 20/40 and the subfoveal macular thickness improved from 706 µm (preoperative) to 221 µm after seven months of follow-up. CONCLUSION: Heads-up digitally assisted viewing technology with I-OCT may be useful or preferred for patients requiring vitreoretinal surgery in the setting of MMS.

Critical analysis of techniques and materials used in devices, syringes, and needles used for intravitreal injections.

Intravitreal injections have become the most commonly performed intraocular treatments worldwide. Because intravitreal injections may induce severe adverse events, such as infectious and noninfectious endophthalmitis, cataract, ocular hypertension, vitreous hemorrhage, or retinal detachment, appropriate awareness of the materials and techniques used are essential to reduce these sight-threatening complications. This review provides insights into the needles, syringes, silicone oil coating, sterilization methods, devices to assist intravitreal injections, scleral piercing techniques using needles, syringe handling, anesthesia, and safety issues related to materials and techniques. It is paramount that physicians be aware of every step involved in intravitreal injections and consider the roles and implications of all materials and techniques used. The ability to understand the theoretical and practical circumstances may definitely lead to state-of-the-art treatments delivered to patients. The most important practical recommendations are: choosing syringes with as little silicone oil as possible, or, preferably, none; avoiding agitation of syringes; awareness that most biologics (e.g., antiangiogenic proteins) are susceptible to changes in molecular properties under some conditions, such as agitation and temperature variation; understanding that improper materials and techniques may lead to complications after intravitreal injections, e.g., inflammation; and recognizing that some devices may contribute to an enhanced, safer, and faster intravitreal injection technique.