ASSESSMENT OF SIMULATED SURGICAL DEXTERITY AFTER MODIFIABLE EXTERNAL EXPOSURES AMONG NOVICE VERSUS EXPERIENCED VITREORETINAL SURGEONS.

PURPOSE: To evaluate novice and senior vitreoretinal surgeons after various exposures. Multiple comparisons ranked the importance of these exposures for surgical dexterity based on experience. METHODS: This prospective cohort study included 15 novice and 11 senior vitreoretinal surgeons (<2 and >10 years' practice, respectively). Eyesi-simulator tasks were performed after each exposure. Day 1, placebo, 2.5 mg/kg caffeine, and 5.0 mg/kg caffeine; day 2, placebo, 0.2 mg/kg propranolol, and 0.6 mg/kg propranolol; day 3, baseline simulation, breathalyzer readings of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentrations; day 4, baseline simulation, push-up sets with 50% and 85% repetitions maximum; and day 5, 3-hour sleep deprivation. Eyesi-generated score (0-700, worst-best), out-of-tolerance tremor (0-100, best-worst), task completion time (minutes), and intraocular pathway (in millimeters) were measured. RESULTS: Novice surgeons performed worse after caffeine (-29.53, 95% confidence interval [CI]: -57.80 to -1.27, P = 0.041) and alcohol (-51.33, 95% CI: -80.49 to -22.16, P = 0.001) consumption. Alcohol caused longer intraocular instrument movement pathways (212.84 mm, 95% CI: 34.03-391.65 mm, P = 0.02) and greater tremor (7.72, 95% CI: 0.74-14.70, P = 0.003) among novices. Sleep deprivation negatively affected novice performance time (2.57 minutes, 95% CI: 1.09-4.05 minutes, P = 0.001) and tremor (8.62, 95% CI: 0.80-16.45, P = 0.03); however, their speed increased after propranolol (-1.43 minutes, 95% CI: -2.71 to -0.15 minutes, P = 0.029). Senior surgeons' scores deteriorated only following alcohol consumption (-47.36, 95% CI: -80.37 to -14.36, P = 0.005). CONCLUSION: Alcohol compromised all participants despite their expertise level. Experience negated the effects of caffeine, propranolol, exercise, and sleep deprivation on surgical skills.

TRANSPLANTATION OF SUBRETINAL STEM CELL-DERIVED RETINAL PIGMENT EPITHELIUM FOR STARGARDT DISEASE: A Phase I Clinical Trial.

PURPOSE: To assess the safety of injecting human embryonic stem cell retinal pigment epithelial cell dose to treat Stargardt disease. METHODS: In this prospective, Phase I clinical trial, human embryonic stem cell retinal pigment epithelial cells in suspension were injected into the subretinal space in eyes with the worse best-corrected visual acuity (BCVA). After vitrectomy/posterior hyaloid removal, a partial retinal detachment was created and the human embryonic stem cell retinal pigment epithelial cells were administered. Phacoemulsification with intraocular lens implantation was performed in eyes with lens opacity. All procedures were optical coherence tomography-guided. The 12-month follow-up included retinal imaging, optical coherence tomography, visual field/electrophysiologic testing, and systemic evaluation. The main outcome was the absence of ocular/systemic inflammation or rejection, tumor formation, or toxicity during follow-up. RESULTS: The mean baseline BCVAs in the phacoemulsification and no phacoemulsification groups were similar (1.950 ± 0.446 and 1.575 ± 0.303, respectively). One year postoperatively, treated eyes showed a nonsignificant increase in BCVA. No adverse effects occurred during follow-up. Intraoperative optical coherence tomography was important for guiding all procedures. CONCLUSION: This surgical procedure was feasible and safe without cellular migration, rejection, inflammation, or development of ocular or systemic tumors during follow-up.

Orbicularis Oculi Muscle Immunohistochemical, Metabolic, and Morphometric Differences in Affected and Nonaffected Sides in Hemifacial Spasm vs Healthy Subjects.

BACKGROUND: Subtle morphological alterations have been reported even in the nonaffected side of the orbicularis oculi muscle in patients with hemifacial spasm. However, no previous study assessed immunohistochemical, metabolic, and morphometric alterations in orbicularis oculi muscle fibers in affected and nonaffected sides in patients with this condition, compared with samples obtained from healthy subjects. The purpose of this study is to objectively assess and compare orbicularis oculi muscle (OOM) samples of hemifacial spasm affected and nonaffected sides and healthy subjects. METHODS: Orbicularis oculi samples from 8 patients with hemifacial spasm who had not been previously treated and 6 healthy subjects were prepared using hematoxylin and eosin, nicotinamide adenine dinucleotide tetrazolium reductase, cytochrome oxidase, succinate dehydrogenase, Gomori staining, and monoclonal antibodies against myosin slow and myosin fast. A digital image analysis software was used for objective analysis. RESULTS: OOM fiber area was significantly greater in both affected ( P = 0.0379) and nonaffected sides ( P = 0.0012) of HFS samples when compared with control subjects' fibers. A significantly greater number of oxidative fibers were observed in both affected and nonaffected sides of patients with HFS when compared with control subjects ( P < 0.001 for both). A significantly greater percentage of slow fibers was observed in the affected side of HFS patients ( P = 0.0012) compared with control subjects. CONCLUSIONS: This study's findings suggest that repeated contractions might lead to OOM fiber hypertrophy, increased mitochondrial metabolism, and possible conversion of fast-twitch orbicularis oculi muscle fibers into slow-twitch fibers in patients with HFS. Alterations were observed in affected and nonaffected sides, confirming initial findings that the nonaffected side is not normal in this unique condition.

Blinking Parameters Do Not Normalize After Botulinum Toxin Therapy in Blepharospasm and Hemifacial Spasm Patients.

BACKGROUND: Little is known regarding changes induced by botulinum toxin injections on blinking parameters in blepharospasm (BSP) and hemifacial spasm (HFS) patients. The purpose of this study was to investigate objective changes induced by botulinum toxin (BoNT) injections on blinking parameters in BSP and HFS patients. METHODS: Thirty-seven patients with BSP and HFS were evaluated before and 30 days after receiving onabotulinumtoxinA injections. Twelve age-matched control subjects were also assessed. Pretreatment and post-treatment parameters were assessed and compared with normal controls. A high-speed camera and microlight-emitting diodes were used to register the blinking in patients and control groups. Outcomes were blinking frequency, amplitude, and maximum velocity of eyelid closure. RESULTS: BoNT injections led to a significant reduction in all parameters, compared with baseline, in BSP and on the affected side in HFS, respectively: 22% ( P < 0.001) and 20% ( P = 0.015) in amplitude; 21% ( P = 0.04) and 39% in frequency ( P = 0.002); and 41% ( P < 0.001) and 26% ( P = 0.005) in maximum closing velocity. Blinking amplitude ( P = 0.017 and P = 0.019) and velocity ( P < 0.001 for both groups) were significantly lower at 30 days on BSP and on the affected HFS side, when compared with controls. BSP and HFS patients presented a significantly lower velocity of eyelid closure, even before BoNT, compared with controls ( P = 0.004. and P < 0.001, respectively). CONCLUSIONS: Although blinking frequency became close to normal, amplitude and velocity after BoNT applications were significantly lower in BSP and on the affected side of HFS patients when compared with age-matched normal controls, demonstrating that blinking parameters do not normalize after treatment. The velocity of eyelid closure was shown to be significantly lower, even before BoNT treatment, when compared with control subjects.

Ocular Findings in Infants with Congenital Toxoplasmosis after a Toxoplasmosis Outbreak.

PURPOSE: We investigated the prevalence of ocular abnormalities in infants vertically exposed to Toxoplasma gondii infection during an outbreak in Santa Maria City, Brazil. DESIGN: Consecutive case series. PARTICIPANTS: A total of 187 infants were included. METHODS: The infants were recruited from January 2018 to November 2019. All mothers were screened for syphilis and human immunodeficiency virus before delivery. Toxoplasmosis infection was confirmed in all mothers and infants based on the presence of serum anti-T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies. All infants underwent an ophthalmologic examination; ocular abnormalities were documented using a wide-field digital imaging system. Neonatal cranial sonography or head computed tomography was performed in 181 infants, and the cerebrospinal fluid (CSF) was screened for anti-T. gondii IgG and IgM antibodies in 159 infants. Peripheral blood samples from 9 infants and their mothers were analyzed for the presence of T. gondii DNA by real-time polymerase chain reaction. MAIN OUTCOME MEASURES: Ocular abnormalities associated with congenital toxoplasmosis. RESULTS: A total of 187 infants were examined. Twenty-nine infants (15.5%) had congenital toxoplasmosis, of whom 19 (10.2%) had ocular abnormalities, including retinochoroiditis in 29 of 38 eyes (76.3%), optic nerve abnormalities in 5 eyes (13.2%), microphthalmia in 1 eye (2.6%), and cataract in 2 eyes (5.3%). Bilateral retinal choroidal lesions were found in 10 of 19 infants (52.6%). Nine eyes of 6 infants had active lesions, with retinal choroidal cellular infiltrates at the first examination. Thirteen (7.2%) of 181 infants screened presented with cerebral calcifications. Eighty-three percent of the screened infants were positive for anti-T. gondii IgG and negative for IgM antibodies in the CSF. Congenital toxoplasmosis was higher in mothers infected during the third pregnancy trimester, and maternal treatment during pregnancy was not associated with a lower rate of congenital toxoplasmosis. CONCLUSIONS: High prevalence rates of clinical manifestations were observed in infants with congenital toxoplasmosis after a waterborne toxoplasmosis outbreak, the largest yet described. Cerebral calcifications were higher in infants with ocular abnormalities, and maternal infection during the third pregnancy trimester was associated with a higher rate of congenital toxoplasmosis independent of maternal treatment.

Two-Year Results of the Phase 3 Randomized Controlled Study of Abicipar in Neovascular Age-Related Macular Degeneration.

PURPOSE: To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). DESIGN: Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data. PARTICIPANTS: The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters. METHODS: At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630). MAIN OUTCOME MEASURES: Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs). RESULTS: For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was -147 µm, -146 µm, and -142 µm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. CONCLUSIONS: Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden.

Clinical and molecular findings in a cohort of 152 Brazilian severe early onset inherited retinal dystrophy patients.

Leber congenital amaurosis (LCA) and early-onset retinal dystrophy (EORD) are severe inherited retinal dystrophy that can cause deep blindness childhood. They represent 5% of all retinal dystrophies in the world population and about 10% in Brazil. Clinical findings and molecular basis of syndromic and nonsyndromic LCA/EORD in a Brazilian sample (152 patients/137 families) were studied. In this population, 15 genes were found to be related to the phenotype, 38 new variants were detected and four new complex alleles were discovered. Among 123 variants found, the most common were CEP290: c.2991+1655A>G, CRB1: p.Cys948Tyr, and RPGRIP1: exon10-18 deletion.

Efficacy and Safety of Abicipar in Neovascular Age-Related Macular Degeneration: 52-Week Results of Phase 3 Randomized Controlled Study.

PURPOSE: To compare the efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) versus ranibizumab every 4 weeks in treatment-naïve patients with neovascular age-related macular degeneration (AMD). DESIGN: Two randomized, multicenter, double-masked, parallel-group, active-controlled, phase 3 clinical trials (CEDAR, SEQUOIA) with identical protocols were conducted. Data from both trials were pooled for analysis. PARTICIPANTS: Patients with active choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) of 24-73 Early Treatment Diabetic Retinopathy Study letters in the study eye were enrolled. METHODS: Patients (n = 1888) were randomized in a 1:1:1 ratio to study eye treatment with abicipar 2 mg every 8 weeks after 3 initial doses at baseline and weeks 4 and 8 (Q8), abicipar 2 mg every 12 weeks after 3 initial doses at baseline and weeks 4 and 12 (Q12), or ranibizumab 0.5 mg every 4 weeks (Q4). MAIN OUTCOME MEASURES: The primary efficacy end point was proportion of patients with stable vision (defined as <15-letter loss in BCVA from baseline) in the study eye at week 52. Secondary end points included change from baseline in BCVA and central retinal thickness (CRT) at week 52. Safety measures included adverse events (AEs). RESULTS: The proportion of patients with stable vision at week 52 was 93.2%, 91.3%, and 95.8% in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively, with both abicipar Q8 and Q12 noninferior to ranibizumab Q4. Week 52 mean change from baseline in BCVA was 7.5, 6.4, and 8.4 letters and in CRT was -144, -145, and -144 µm in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. Incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3%, respectively. The IOI AEs were typically mild or moderate in severity and treated with topical corticosteroids; 62 of 192 patients (32.3%) received oral and/or injectable corticosteroids. CONCLUSIONS: Abicipar Q8 and Q12 were both noninferior to ranibizumab Q4 in the primary end point of stable vision at week 52. Intraocular inflammation was more frequent with abicipar. Quarterly and Q8 abicipar reduce nAMD disease and treatment burden compared with monthly treatment.

Evaluation of botulinum toxin effects in hemifacial spasm patients: correlation between clinical rating scales and high-speed video system measurements.

The purpose of this study was to compare the scores of two clinical rating scales and high-speed video system measurements obtained during spontaneous eyelid movements in hemifacial spasm (HFS) patients before and after treatment. Patients were evaluated before and 30 days after receiving treatment with onabotulinumtoxinA injections. Using a high-speed video system, the eyelid movements were recorded bilaterally for 3 min and the energy power generated by the upper eyelid during spontaneous eyelid movements was assessed before and after treatment. The scores of the Jankovic rating scale (JRS) and Hemifacial Spasm Grading System (HSGS) were also assessed before and after treatment. The authors studied 22 patients. Significant reduction in JRS and HSGS scores and in the energy generated by the upper eyelid was observed after treatment. A power spectrum of less than 23,000 was associated with JRS and HSGS scores less than 4 and 6.25, respectively and a power spectrum greater than or equal to 23,000 was associated with JRS and HSGS scores greater than or equal to 4 and 6.25, respectively (p < 0.0001 and p = 0.0025). Rating systems are easy to use, but they may exhibit limitations in sensitivity to assess differences between distinct disease patterns and between subtle differences in treatment responses. The high-speed video system permits a greater degree of accuracy, which allows for the assessment of differences in eyelid movement patterns and would permit better tailoring of treatment to patients. However, simpler devices employing this system would need to be developed, so that it could be used in clinical practice.

Analysis of blink activity and anomalous eyelid movements in patients with hemifacial spasm.

To assess spontaneous blinking and anomalous eyelid movements in patients with hemifacial spasm with an emphasis on interocular differences. Spontaneous eyelid movements were registered bilaterally for 3 min using a high-speed video camera in 28 patients with hemifacial spasm (HFS) who had not been treated with botulinum toxin injections for at least 5 months. The degree of blink conjugacy, maximum velocity, and amplitude of the closing phase of the blinks were determined for the affected and non-affected sides. Out of the 28 subjects, 23 (82%) presented with abnormal nonconjugate spasms that were similar to blinks, and in 17 (61%), high-frequency eyelid twitches were detected between blinks on the affected eye. The rate of nonconjugate blink-like spasms ranged from 0.3 to 24.7 movements/min. With regard for conjugate blinks, there was no significant interocular difference in amplitudes or eyelid closure velocities. The amplitude and velocity were significantly lower for nonconjugate movements than for spontaneous blinks. HFS is a unique condition in which complex patterns of eyelid movements, including both conjugate and nonconjugate movements, are present. Conjugate movements correspond to spontaneous blinking, and the same metrics were observed in affected and non-affected eyes. Nonconjugate movements correspond to anomalous nonconjugate blink-like spasms and high-frequency eyelid twitches in the affected eye, both of which were characterized by lower amplitudes and velocities than were observed in conjugate movements.

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.

Orbicularis Oculi Morphological Alterations in Affected and Nonaffected Sides in Hemifacial Spasm.

BACKGROUND: Although the nonaffected side appears to be clinically normal in hemifacial spasm (HFS), it is not known whether this side can be considered normal regarding histopathological findings. The purpose of this study was to objectively evaluate and compare orbicularis oculi samples of patients with HFS (not previously treated with botulinum toxin) and control patients undergoing cosmetic upper eyelid blepharoplasty. METHODS: Orbicularis oculi samples from 22 eyelids were evaluated. There were 7 samples from the affected and 7 samples from the nonaffected sides of patients with HFS who had not been previously treated with botulinum toxin, and 8 samples from normal control patients. Muscle samples were prepared using hematoxylin and eosin staining, and a digital image analysis software was used for objective analyses. RESULTS: When compared with normal controls, endomysial and perimysial connective tissue areas were significantly increased (P = 0.015) on the affected side in HFS, suggesting that this disorder is associated with chronic alterations that lead to muscle degeneration. Cell density was significantly reduced on the affected (P = 0.028) and also on the nonaffected sides in HFS (P = 0.003) compared with normal controls. This was observed, although, clinically, there were no signs or symptoms of increased muscular contraction on the nonaffected sides in any of the patients with HFS studied. CONCLUSIONS: Significant morphological differences in the orbicularis oculi muscle in patients with HFS were observed on both the affected and nonaffected sides. Our findings suggest a potential role for muscle homeostasis disturbances on both sides for patients with HFS. Affected sides in patients with HFS did, however, demonstrate muscle degeneration that was not present on the nonaffected sides.

Comparative Analysis of Functional and Structural Decline in Retinitis Pigmentosas.

Retinitis pigmentosa (RP) is a category of inherited retinal dystrophies that is best prognosticated using electroretinography (ERG). In this retrospective cohort study of 25 patients with RP, we evaluated the correlation between 30 Hz flicker ERG and structural parameters in the retina. Internationally standardized 30 Hz flicker ERG recordings, short-wavelength autofluorescence (SW-AF), and spectral domain-optical coherence tomography (SD-OCT) were acquired at two visits at least one year apart. Vertical and horizontal hyperautofluorescent ring diameter measurements with SW-AF, as well as ellipsoid zone (EZ) line width measurements with SD-OCT, were used as structural parameters of disease progression. The 30 Hz flicker ERG amplitude decreased by 2.2 ± 0.8 µV/year (p = 0.011), while implicit times remained unchanged. For SD-OCT, the EZ line decreased by 204.1 ± 34.7 µm/year (p < 0.001). Horizontal and vertical hyperautofluorescent ring diameters decreased by 161.9 ± 25.6 µm/year and 146.9 ± 34.6 µm/year, respectively (p = 0.001), with SW-AF. A correlation was found between the progression rates of the 30 Hz flicker amplitude recorded with Burian-Allen electrodes and both the horizontal ring diameter (p = 0.020) and EZ line (p = 0.044). SW-AF and SD-OCT, two readily available imaging techniques, may be used to prognosticate disease progression because of the reliability of their measurements and correlation with functional outcome.

Natural history of diabetic macular edema and factors predicting outcomes in sham-treated patients (MEAD study).

PURPOSE: To describe the natural history of diabetic macular edema (DME) with respect to best-corrected visual acuity (BCVA) and central retinal thickness (CRT) outcomes and to identify baseline patient characteristics and systemic factors associated with improvement or worsening of outcomes in sham-treated patients. METHODS: The study population was sham-treated patients (n = 350) in the 3-year MEAD registration study of dexamethasone intravitreal implant for treatment of DME. Patients had center-involved DME and received sham intravitreal injections in the study eye at ≥ 6-month intervals. Potential prognostic factors for outcomes were evaluated using multiple linear regression analysis. RESULTS: Visual and anatomic outcomes were poorer in patients who left the study early (n = 198) than in study completers (n = 152). Mean change in BCVA from baseline at the last visit with available data was + 0.9 letters; 37.5% of patients had no change in BCVA, 23.2% had gained > 10 letters, and 16.0% had lost > 10 letters. Older age and baseline diabetic retinopathy score > 6 were associated with worse BCVA outcomes; thicker baseline CRT and larger number of hypertension medications used were associated with larger reductions in CRT during the study. CONCLUSIONS: BCVA and CRT outcomes were variable in this population of DME patients with generally good glycemic control. In DME patients without active treatment, older age and baseline diabetic retinopathy score > 6 were associated with less improvement in BCVA; thicker baseline CRT and a larger number of antihypertensive medications used predicted better improvement in CRT. TRIAL REGISTRATION: The MEAD study trials are registered at ClinicalTrials.gov with the identifiers NCT00168337 and NCT00168389.

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative.

TOPIC: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. CLINICAL RELEVANCE: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. METHODS: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. RESULTS: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. CONCLUSIONS: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents.

Peptidyl-prolyl cis-trans isomerase A - A novel biomarker of multi-episodic (recurrent) ocular toxoplasmosis.

Ocular toxoplasmosis (OT) is the most common etiology of posterior uveitis. The high incidence of macular scarring associated with OT is a leading cause of visual morbidity. Serum biomarkers of the disease would aid in its diagnosis. This study sought, for the first time, to elucidate serum biomarkers for OT by mass spectrometry. Blood samples were collected from four groups of nine patients each; toxoplasmosis IgG-with no history of uveitis, non-toxoplasmosis uveitis, first episode OT, and symptomatic recurrent OT. Serum was isolated and subjected to proteomics analysis using 2-dimensional gel electrophoresis (2D-GE) and surface-enhanced laser desorption ionization mass spectrometry (SELDI-MS). Selected proteins were further separated by SDS-PAGE and sequenced using tandem MS. Results were cross-validated with a T. gondii outbreak biomarker database that occurred in Brazil. Fifty markers of OT and 46 markers of recurrent disease were discovered by SELDI-MS of which 30 and 15, respectively, were cross-validated. 2D-GE analysis yielded 57 bands, selected based on the intensity of the bands, leading to the identification of 20 proteins. Eleven of those identified candidates were also found by SELDI-MS. Four candidates were chosen for immunoblotting. One serum protein, peptidyl-prolyl cis-trans isomerase A (PPIA), was confirmed as a biomarker of multi-episodic OT by immunoblotting in patients. PPIA can identify the patient with active recurrent OT from acute OT, other forms of uveitis and other parasitic infections. A validated PPIA assay may have a role in the diagnosis of the atypical OT patient before more invasive anterior chamber or vitreous tap is performed for PCR analysis or for Goldmann-Witner coefficient calculations. Base-line PPIA levels need to be studied to understand its possible use when deciding for prophylactic antibiotic use in the immunosuppressed sero-positive patient.

Prevalence of Toxoplasma gondii DNA in Processed Pork Meat.

Toxoplasma gondii infection may be attributed to the ingestion of pork meat and contaminated water. In southern Brazil, the prevalence of blindness caused by T. gondii is the highest in the world. Our purpose is to determine the frequency of T. gondii DNA in commercial fresh sausage and cured salami samples from Rio Grande do Sul state, south of Brazil. A total of 118 samples (sausage and salami) from 8 different producers were collected and DNA was extracted. Real-time polymerase chain reaction (qPCR) technique was performed to detect T. gondii DNA using B1 marker. The frequency of T. gondii DNA among the total number of samples (sausage and salami) was 39% (46/118). Among these, a higher frequency of positivity was observed in the sausage samples (47.5%) when compared with the salami samples (17%). However, the mean parasite concentration was significantly higher in the salami samples. The prevalence of T. gondii DNA in fresh sausage and cured salami may indicate that infected pigs may be an important source of infections and a public health hazard to be considered.

Natural History of Conversion of Leber's Hereditary Optic Neuropathy: A Prospective Case Series.

PURPOSE: To illustrate the natural history of Leber's hereditary optic neuropathy (LHON). DESIGN: Prospective observational case series. PARTICIPANTS: The Soave-Brazil pedigree of m.11778G>A/ND4 mitochondrial DNA LHON mutation. METHODS: A prospectively acquired database of the Soave-Brazil pedigree was reviewed. Data from 285 individuals were included in the database over a 15-year period. The pedigree was reviewed for unaffected mutation carriers who converted to affected status, 6 patients with LHON were identified. The medical records were reviewed 1 year preconversion to 1 year postconversion for visual acuity (logarithm of the minimum angle of resolution [logMAR]), Humphrey Visual Field (HVF) mean deviation (MD), and retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus (Carl Zeiss, Oberkochen, Germany) optic coherence tomography (OCT). The RNFL thickness values were normalized for age. Visual acuity, HVF, and processed RNFL data from each of the 12 eyes were then sorted into 2-month time periods relative to the date of conversion, within which they were averaged. MAIN OUTCOME MEASURES: The main outcome measures were visual acuity, HVF MD, and RNFL thickness. RESULTS: Decreased visual acuity preceded conversion by up to 2 months and then declined up to 8 months postconversion. Decrease in HVF MD occurred at least 4 months preceding conversion, after which values decreased until plateau at 6 to 8 months. Average RNFL thickness was above normal baseline thickness in all 4 quadrants as measured by OCT at the time of conversion. Increase in RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. The temporal quadrant was first to be involved, then the inferior and superior quadrants, and the nasal quadrant showed the latest and least changes. CONCLUSIONS: Subclinical changes preceded the date of conversion and may reflect the complicated nature of identifying the date of conversion in LHON. Early increases in RNFL preceding conversion suggest that structural changes precede clinically significant vision loss. Asynchronous quadrant involvement supports a previously published mathematical model. The natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau.

Zika virus and the eye.

PURPOSE OF REVIEW: The aim of this study was to review the ocular findings related to the Zika virus (ZIKV) based on the main studies published to date, describe the patterns of the lesions and risk factors, and identify the public health implications and scientific importance of this emerging disease. RECENT FINDINGS: In most studies, the ZIKV seems related to congenital ocular lesions and most mothers reported mild symptoms during the first pregnancy trimester. Five fundus patterns were seen most often: macular chorioretinal atrophy, chorioretinal atrophy elsewhere, focal pigmentary changes in the macular region, optic nerve abnormalities and combined types. A few studies have suggested that the ZIKV might damage the anterior segment of these babies' eyes. Few reports have described the ocular complications seen in adults during the acute infection, including conjunctivitis, iridocyclitis and chorioretinitis. SUMMARY: Infants with congenital Zika syndrome might have vision-threatening fundus abnormalities. Although the full spectrum of ocular lesions caused by the ZIKV infection is not yet determined, a distinctive new disease has been observed. Recognition of these lesions by ophthalmologists can help ensure appropriate etiologic evaluation and clinical investigation to define the range of anomalies in an affected infant and determine essential follow-up and ongoing care.