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.

The effect of bevacizumab, 5-fluorouracil, and triamcinolone on the healing modulation of surgical wounds in rats.

In this study, we aimed to analyze the effect of 5-fluorouracil, triamcinolone, and bevacizumab on scar modulation in an experimental rat model of surgical lesions. Rats (Rattus norvegicus albinus) were divided into four groups: bevacizumab, 5-fluorouracil + triamcinolone, bevacizumab + 5-fluorouracil + triamcinolone, and control (received no medication) groups. A linear, dorsal incision was created and sutured for the first intention wound healing, mimicking the surgical incision of upper blepharoplasty. Treatments were initiated on day 7, and the rats were euthanized on day 14. Only in the 5-fluorouracil + triamcinolone group was there a difference in the number of infiltrated monocytes. There was 56%, 86%, and 85% decrease in the number of neovessels in the bevacizumab, 5-fluorouracil + triamcinolone, and bevacizumab + 5-fluorouracil + triamcinolone groups, respectively, compared with the control. Picrosirius red staining showed higher collagen density and more organized collagen in the treatment groups than in the control group. Scar modulation was observed in all groups, but the 5-fluorouracil + triamcinolone group presented the best results. To our knowledge, this is the first study to evaluate the influence of three medications in combination on healing. When used together, these medications can prevent the development of unsightly scars, and are therefore promising alternatives to corticosteroids.

Risk of adverse pregnancy and infant outcomes associated with prenatal Zika virus infection: a post-epidemic cohort in Central-West Brazil.

This study aimed to estimate the risks of adverse infant outcomes in the first year of life related to prenatal Zika virus (ZIKV) exposure. A prospective cohort of pregnant women with rash was recruited in Central-West Brazil in a post-epidemic period (January 2017 to April 2019). We evaluated participants' medical histories and performed ZIKV diagnostic testing using molecular (reverse transcription polymerase chain reaction [RT-PCR]) and serologic (immunoglobulin [Ig]M and plaque reduction neutralization tests [PRNT90]) assays. The ZIKV-positive group included both RT-PCR-confirmed cases as well as IgM and/or PRNT90-positive probable cases. Children were evaluated at birth and in the first 12 months of life. Transfontanellar ultrasound, central nervous system computed tomography, eye fundoscopy and retinography were performed. We estimated the absolute risk and 95% confidence interval (95% CI) of adverse infant outcomes among confirmed prenatally ZIKV-exposed children. Among 81 pregnant women with rash, 43 (53.1%) were ZIKV infected. The absolute risk of microcephaly among offspring of ZIKV-infected pregnant women was 7.0% (95% CI: 1.5-19.1), including the two cases of microcephaly detected prenatally and one detected postnatally. In total, 54.5% (95% CI: 39.8-68.7) of children in the ZIKV-exposed group had at least one ophthalmic abnormality, with the most frequent abnormalities being focal pigmentary mottling and chorioretinal atrophy or scarring. Our findings reinforce the importance of long-term monitoring of prenatally ZIKV-exposed children born apparently asymptomatic for Congenital Zika Syndrome.

Analysis of cytokines in the aqueous humor during intravitreal Ranibizumab treatment of diabetic macular edema.

This study aimed to analyze the concentrations of VEGF, b-FGF, TNF, interleukin (IL)-1, IL-6, IL-8, IL-10, and IL-12 in the aqueous humor of patients with diabetic macular edema with and without peripheral retinal ischemia and to ascertain the changes in the levels of these molecules during treatment with ranibizumab. A therapeutic, prospective, randomized interventional study was carried out. Twenty-four eyes from 24 patients were studied and divided into 3 groups. Group 1 (9 eyes) included patients with diabetic macular edema without peripheral ischemia. Group 2 (10 eyes) included patients with diabetic macular edema with peripheral ischemia. Group 3 (5 eyes), the control group, included patients without systemic and/or eye diseases. Patients in Groups 1 and 2 received 3 intravitreal injections of 2 mg/0.05 ml ranibizumab at an interval of approximately 30 days. Before administering the injections, the aqueous humor was collected. In the control group, aqueous humor was collected before facetectomy. During treatment, the median IL-6 concentration significantly increased in Group 1 but showed a slight but not significant decrease in Group 2. Interleukin 8 levels were significantly different at the end of treatment compared to the beginning in Groups 1 and 2. TNF, IL-1, IL-10, and IL-12 levels were practically unchanged in both groups. VEGF was significantly reduced at the end of the study in Groups 1 and 2. B-FGF was not detected in most of the studied patients, and in those with detectable levels, there was no significant variation. There was a significant increase in the median level of interleukin 6 in the group without ischemia and a significant decrease in VEGF in both groups. The cytokines TNF, IL-1, IL-10, and IL-12 did not show significant variation.

Novel Possible Protein Targets in Neovascular Age-Related Macular Degeneration: A Pilot Study Experiment.

Age-related macular degeneration (AMD) is among the world's leading causes of blindness. In its neovascular form (nAMD), around 25% of patients present further anatomical and visual deterioration due to persistence of neovascular activity, despite gold-standard treatment protocols using intravitreal anti-VEGF medications. Thus, to comprehend, the molecular pathways that drive choroidal neoangiogenesis, associated with the vascular endothelial growth factor (VEGF), are important steps to elucidate the mechanistic events underneath the disease development. This is a pilot study, a prospective, translational experiment, in a real-life context aiming to evaluate the protein profiles of the aqueous humor of 15 patients divided into three groups: group 1, composed of patients with nAMD, who demonstrated a good response to anti-VEGF intravitreal injections during follow-up (good responsive); group 2, composed of patients with anti-VEGF-resistant nAMD, who demonstrated choroidal neovascularization activity during follow-up (poor/non-responsive); and group 3, composed of control patients without systemic diseases or signs of retinopathy. For proteomic characterization of the groups, mass spectrometry (label-free LC-MS/MS) was used. A total of 2,336 proteins were identified, of which 185 were distinctly regulated and allowed the differentiation of the clinical conditions analyzed. Among those, 39 proteins, including some novel ones, were analyzed as potential disease effectors through their pathophysiological implications in lipid metabolism, oxidative stress, complement system, inflammatory pathways, and angiogenesis. So, this study suggests the participation of other promising biomarkers in neovascular AMD, in addition to the known VEGF.

Pedicle internal limiting membrane flap technique for very large macular holes: a preliminary report.

BACKGROUND: Conventional vitrectomy technique for macular hole surgery has a good outcome in small and medium macular holes, but for very large macular holes (minimum linear diameter higher than 700 µm) other techniques were developed aiming to achieve greater rates of closure and visual acuity gain. The purpose of this article is to report the anatomical and functional outcomes of four very large macular hole (MH) cases which have undergone vitrectomy with the pedicle internal limiting membrane (ILM) flap technique. METHODS: This is a retrospective series of four patients with large MH who were treated with vitrectomy and the pedicle ILM flap technique. Comprehensive ophthalmologic evaluation was performed before surgery and included ETDRS best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography (SD-OCT) for MH measures: height, minimum linear diameter (MLD) and external base diameter. The particular detail of this technique is related to ILM flap creation. During the peeling, the ILM was not removed completely from the retina but was left attached to the edges of the macular hole and subsequently trimmed with the vitrectomy probe using the scissors mode. RESULTS: Four patients with very large MH underwent PPV and the pedicle ILM flap technique was used to pursue macular closure. Median preoperative BCVA was 20/400 (range: 20/320 to 20/400) and median postoperative BCVA was 20/200 (range: 20/320 to 20/200). Of the 4 cases reported, 3 obtained anatomical closure (75%), and also presented BCVA improvement after surgery, considering the last follow-up visit of each case. No additional procedures were performed in either case. One patient demonstrated no anatomic and functional improvement. CONCLUSION: The present study describes the first Brazilian case series of very large MH treated by the inverted pedicle ILM flap technique. This technique was associated with anatomic and visual improvement in most cases, and represents an alternative therapeutic approach for large macular holes.Trial Registration Project registered in Plataforma Brasil with CAAE number 30163520.0.0000.5440 and approved in ethics committee   from  Ribeirão Preto Medical School Clinics Hospital, University of São Paulo-Ribeirão Preto, São Paulo, Brazil (appreciation number 3.948.426 gave the approval).

In vivo and in vitro toxicity evaluation of liposome-encapsulated sirolimus.

BACKGROUND: To evaluate the in vivo and in vitro toxicity of a new formulation of liposome-encapsulated sirolimus (LES). METHODS: In vitro experiments were done using ARPE-19 and HRP cells. An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. In vivo experiments were conducted on New Zealand albino rabbits that received intravitreal injections of empty liposomes (EL) or different concentrations of LES. Histopathological and immunohistochemical analyses were performed on the rabbit's eyes following injection. RESULTS: Eighteen eyes of nine rabbits were used. MTT assay cell viability was 95.04% in group 1 (12.5 µL/mL LES). 92.95% in group 2 (25 µL/mL LES), 91.59% in group 3 (50 µL/mL LES), 98.09% in group 4 (12.5 µL/mL EL), 95.20% on group 5 (50 µL/mL EL), 98.53% in group 6 (50 µL/mL EL), and 2.84% on group 8 (50 µL/mL DMSO). There was no statistically significant difference among groups 1 to 7 in cell viability (p = 1.0), but the comparison of all groups with group 8 was significant (p < 0.0001). The TUNEL assay comparing two groups was not statistically significant from groups 1 to 7 (p = 1.0). The difference between groups 1 to 7 and group 8 (p < 0.0001) was significant. Histopathological changes were not found in any group. No activation of Müller cells was detected. CONCLUSION: A novel formulation of LES delivered intravitreally did not cause in vitro toxicity, as evaluated by MTT and TUNEL assays, nor in vivo toxicity as evaluated by histopathology and immunohistochemistry in rabbit eyes.

Macular pigment optical density in a Brazilian sample.

BACKGROUND: To evaluate macular pigment optical density (MPOD) and to identify its determinants in a sample of Brazilian individuals. METHODS: This was a cross-sectional study. One hundred three healthy individuals had both eyes photographed using a Visucam 500 digital fundus camera (Carl Zeiss Meditec, Jena, Germany) in combination with the MPOD module. Four variables were obtained: maximum MPOD, mean MPOD, MPOD volume, and MPOD area. Demographic data and information on lifestyle habits were also collected. RESULTS: Mean MPOD was 0.14 density unit ± 0.05. MPOD was not influenced by gender, smoking history, or refractive error. MPOD was significantly higher among black individuals than among white and biracial individuals. There was a positive but low correlation between MPOD and age. CONCLUSION: This study found MPOD values to be similar to those found in European samples but lower than other studies performed on Asian and Australian samples. This is the first data regarding MPOD in a South American Population.

Clinical outcomes after implantation of a new intrastromal corneal ring with 140-degree of arc in patients with corneal ectasia.

AIM: To evaluate the clinical and tomographic outcomes after implantation of a new intrastromal corneal ring segment (ICRS) with 140-degrees of arc in eyes with corneal ectasia. METHODS: We evaluated patients with corneal ectasia implanted with Ferrara 140° ICRS from April 2010 to February 2015. Outcome measures included preoperative and postoperative corrected distance visual acuity (CDVA), keratometry simulated (K) reading, tomographic astigmatism and asphericity. All patients were evaluated using the Pentacam Scheimpflug system. RESULTS: The study evaluated 58 eyes. The mean follow-up was 16.81±10.8mo. The CDVA (logMAR) improved from 0.5±0.20 (20/60) to 0.3±0.21 (20/40) (P<0.01). The average K reduced from 49.87±7.01 to 47.34±4.90 D (P<0.01). The asphericity changed from -0.60±0.86 to -0.23±0.67 D (P<0.01). The mean preoperative tomographic astigmatism decreased from -8.0±3.45 to -4.53±2.52 D (P<0.01). CONCLUSION: The new ICRS model with 140-degrees of arc effectively improve the visual acuity and reduce the high astigmatism usually found in patients with corneal ectasia.

Comparison between the 1% and 2% ibopamine provocative test in primary open-angle glaucoma patients: sensitivity, specificity and tolerability.

PURPOSE: To compare intraocular pressure (IOP) rise in normal individuals and primary open-angle glaucoma patients and the safety and efficacy of ibopamine eye drops in different concentrations as a provocative test for glaucoma. METHODS: Glaucoma patients underwent (same eye) the ibopamine provocative test with two concentrations, 1% and 2%, in a random sequence at least 3 weeks apart, but not more than 3 months. The normal individuals were randomly submitted to one of the concentrations of ibopamine (1% and 2%). The test was considered positive if there was an IOP rise greater than 3 or 4 mmHg at 30 or 45 minutes to test which subset of the test has the best sensitivity (Se)/specificity (Sp). RESULTS: There was no statistically significant difference in any of the IOP measurements, comparing 1% with 2% ibopamine. The IOP was significantly higher at 30 and 45 minutes with both concentrations (p < 0.001). The best sensitivity/specificity ratio was achieved with the cutoff point set as greater than 3 mmHg at 45 minutes with 2% ibopamine (area under the ROC curve: 0.864, Se: 84.6%; Sp:73.3%). All patients described a slight burning after ibopamine's instillation. CONCLUSION: 2% ibopamine is recommended as a provocative test for glaucoma. Because both concentrations have similar ability to rise IOP, 1% ibopamine may be used to treat ocular hypotony.

Correlation between the ibopamine provocative test and the diurnal tension curve in glaucoma patients.

PURPOSE: To correlate the ibopamine provocative test with the diurnal tension curve (highest intraocular pressure-IOP and range) in glaucoma. METHODS: This is a prospective case series including glaucoma patients from the Federal University of Goiás, Glaucoma Service. Two 2% ibopamine eyedrops were instilled into one or both eyes of each patient, 5 minutes apart. Intraocular pressure was checked before and 30 and 45 minutes after the second ibopamine instillation. Thereafter, the diurnal tension curve of each patient was assessed with five independent measurements (at every 2:30 hours), from 8:00 o'clock AM to 6:00 o'clock PM. Pearson's correlation coefficient was used to test the linear relation between the intraocular pressure after the ibopamine instillation with the highest intraocular pressure value and the intraocular pressure range in the diurnal curve. RESULTS: Thirty-one eyes from 22 patients were included. There was a significant correlation between the intraocular pressure 30 and 45 minutes after ibopamine instillation and the highest intraocular pressure assessed in the diurnal curve (r=0.356, p=0.04 and r=0.429, p=0.01, respectively). However, no correlation between IOP after the use of ibopamine and the diurnal intraocular pressure range at 30 (r=0.046, p=0.8) and 45 minutes (r=0.109, p=0.5) was observed. CONCLUSION: The ibopamine provocative test shows a significant correlation with the highest intraocular pressure in the diurnal tension curve in glaucoma patients. However, no correlation was observed with the intraocular pressure range.

Comparison of Needle Path, Anesthetic Dispersion, and Quality of Anesthesia in Retrobulbar and Peribulbar Blocks.

BACKGROUND AND OBJECTIVES: To compare the needle path during retrobulbar ophthalmic block with that during peribulbar ophthalmic block, its relation with anesthetic spread, and the quality of the anesthesia. METHODS: This is a prospective comparative study in selected candidates of ophthalmic blocks for phacoemulsification. The procedure used a 22-gauge 1 needle in a single lateral inferior transcutaneous puncture with 5 mL of anesthetic solution with radiological contrast. Patients were randomly divided into 2 groups: GI, retrobulbar block; GII, peribulbar block. Computed tomography scans of the orbit were performed at the time of the blockade and 10 minutes after anesthetic injection. The quality of anesthesia was assessed by measurement of ocular motility at 3, 5, and 10 minutes after the block. RESULTS: Twenty eyes per group were included. The needle path was intraconal in 10 cases in GI and in no patient in GII, transfixed the muscle cone in 5 cases in GI and in 4 in GII, and was extraconal in 2 cases in GI and in 13 in GII. The anesthetic dispersion was directly related to the needle path. In all extraconal cases, the block was unsatisfactory. It was satisfactory when the path of the needle was intraconal or the cone was transfixed (P = 1.0). The quality of anesthesia was higher in the retrobulbar block (P < 0.01). CONCLUSIONS: The path of the needle contributed to the orbital anesthetic solution dispersion and the quality of anesthesia. The retrobulbar block technique provided better-quality anesthesia compared with the peribulbar one.

A comparative study between 25 x 0.70 mm and 20 x 0.55 mm needles for retrobulbar block with small volume of anesthetic for the treatment of cataracts by phacoemulsification.

BACKGROUND AND OBJECTIVES: The objective of this study was to compare the quality and safety of retrobulbar block for the treatment of cataracts by phacoemulsification using needles of different sizes: 27 x 0.70 mm and 20 x 0.55 mm. METHODS: Candidates for ophthalmic block for the treatment of cataracts by phacoemulsification were selected prospectively. After sedation and standardized monitoring, a retrobulbar block with 4 mL of 1% ropivacaine containing hyaluronidase was performed with a single inferolateral puncture. In Group I (GI), the 25 x 0.70 mm needle was used, while in Group II (GII) a 20 x 0.55 mm needle was used. All patients had a CT scan at the time of the blockade and five minutes after the administration of the anesthetic solution with radiologic contrast. Ocular mobility was assessed after three, five, and ten minutes. The incidence of complications in both groups and the satisfaction of patients and surgeons were compared by applying a standardized questionnaire. RESULTS: Fifty-four adult patients were evaluated (27 per group). Patients did not complain of intraoperative pain or perception of light. The anesthetic procedure was considered very good (VG) or excellent (E) in 96.3% of the cases in both groups. All patients were subjected to the same assessment. The need of block repetition between both groups did not differ (p = 1.0). Patients in GI showed decreased ocular mobility at 3 minutes (p = 0.03). The intraconal retrobulbar placement of the needle was observed on both groups. Anesthetic dispersion at 5 minutes was similar in the two groups. CONCLUSIONS: Retrobulbar block with a single inferolateral puncture with a 20 x 0.55 mm needle, using low doses of anesthetics, is an effective and safe option for the treatment of cataracts by phacoemulsification.