Pediatric Optic Pathway Gliomas Resource Utilization and Prevalence in the OptumLabs Data Warehouse.

BACKGROUND: Although significant progress has been made in improving the rate of survival for pediatric optic pathway gliomas (OPGs), data describing the methods of diagnosis and treatment for OPGs are limited in the modern era. This retrospective study aims to provide an epidemiological overview in the pediatric population and an update on eye care resource utilization in OPG patients using big data analysis. METHODS: Using the OptumLabs Data Warehouse, 9-11 million children from 2016 to 2021 assessed the presence of an OPG claim. This data set was analyzed for demographic distribution data and clinical data including average ages for computed tomography (CT), MRI, strabismus, and related treatment (surgery, chemotherapy, and radiation), as well as yearly rates for optical coherence tomography (OCT) and visual field (VF) examinations. RESULTS: Five hundred fifty-one unique patients ranging in age from 0 to 17 years had an OPG claim, with an estimated prevalence of 4.6-6.1 per 100k. Among the 476 OPG patients with at least 6 months of follow-up, 88.9% had at least one MRI and 15.3% had at least one CT. Annual rates for OCT and VF testing were similar (1.26 vs 1.35 per year), although OCT was ordered for younger patients (mean age = 9.2 vs 11.7 years, respectively). During the study period, 14.1% of OPG patients had chemotherapy, 6.1% had either surgery or radiation, and 81.7% had no treatment. CONCLUSIONS: This study updates OPG demographics for the modern era and characterizes the burden of the treatment course for pediatric OPG patients using big data analysis of a commercial claims database. OPGs had a prevalence of about 0.005% occurring equally in boys and girls. Most did not receive treatment, and the average child had at least one claim for OCT or VF per year for clinical monitoring. This study is limited to only commercially insured children, who represent approximately half of the general child population.

BIOMARKERS OF MATERNAL SMOKING AND THE RISK OF RETINOBLASTOMA IN OFFSPRING.

PURPOSE: Previous studies examining the risk of retinoblastoma with maternal smoking were inconclusive, likely due in part to the reliance on self-reported maternal smoking. This study uses biomarkers of tobacco smoking in neonatal dried blood spots to investigate associations between maternal smoking and retinoblastoma in offspring. METHODS: The authors randomly selected 498 retinoblastoma cases and 895 control subjects born between 1983 and 2011 from a population-based case-control study in California. Maternal pregnancy-related smoking was measured using the following three metrics: provider or self-reported smoking during pregnancy, cotinine, and hydroxycotinine in neonatal blood. The authors used multivariable logistic regression to estimate the effects of maternal tobacco smoking on retinoblastoma. RESULTS: Using all metrics (biomarkers or self-report), maternal smoking late in pregnancy or early postpartum was related to retinoblastoma (all types; odds ratio = 1.44, 95% confidence interval: 1.00-2.09). Relying on cotinine or hydroxycotinine to ascertain smoking, maternal smoking was related to unilateral retinoblastoma (odds ratio = 1.66, 95% confidence interval: 1.08-2.57). CONCLUSION: The results indicate that maternal smoking during pregnancy may be a risk factor for retinoblastoma, particularly among unilateral cases.

Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis after intraocular procedure.

BACKGROUND: Endophthalmitis refers to severe infection within the eye that involves the aqueous humor or vitreous humor, or both, and that threatens vision. Most cases of endophthalmitis are exogenous (i.e. due to inoculation of organisms from an outside source), and most exogenous endophthalmitis is acute and occurs after an intraocular procedure. The mainstay of treatment is emergent administration of broad-spectrum intravitreous antibiotics. Due to their anti-inflammatory effects, steroids in conjunction with antibiotics have been proposed as being beneficial in endophthalmitis management. OBJECTIVES: To assess the effects of antibiotics combined with steroids versus antibiotics alone for the treatment of acute endophthalmitis following intraocular surgery or intravitreous injection. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 8), MEDLINE Ovid (1946 to August 2021), Embase Ovid (1980 to August 2021), LILACS (Latin American and Caribbean Health Sciences Literature database) (1982 to August 2021), the ISRCTN registry; searched August 2021, ClinicalTrials.gov; searched August 2021, and the WHO International Clinical Trials Registry Platform; searched August 2021. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing the effectiveness of adjunctive steroids with antibiotics alone in the management of acute, clinically diagnosed endophthalmitis following intraocular surgery or intravitreous injection. We excluded trials with participants with endogenous endophthalmitis unless outcomes were reported by source of infection. We imposed no restrictions on the method or order of administration, dose, frequency, or duration of antibiotics and steroids. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology, and graded the certainty of the body of evidence for six outcomes using the GRADE classification. MAIN RESULTS: We included four RCTs with a total of 264 eyes of 264 participants in this review update. The studies were conducted in South Africa, India, and the Netherlands. All studies used intravitreous dexamethasone for adjunctive steroid therapy and a combination of two intravitreous antibiotics that provided gram-positive and gram-negative coverage for the antibiotic therapy. We judged two trials to be at overall low risk of bias, and the other two studies to be at overall unclear risk of bias due to lack of reporting of study methods. Only one study was registered in a clinical trial register.  While none of the included studies reported the primary outcome of complete resolution of endophthalmitis as defined in our protocol, one study reported combined anatomical and functional success (i.e. proportion of participants with intraocular pressure of at least 5 mmHg and visual acuity of at least 6/120). Very low certainty evidence suggested no difference in combined success when comparing adjunctive steroid to antibiotics alone (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.80 to 1.45; 32 participants). Low certainty evidence from two studies suggested that adjunctive dexamethasone may result in having a good visual outcome (Snellen visual acuity 6/6 to 6/18) at 3 months compared with antibiotics alone (RR 1.95, 95% CI 1.05 to 3.60; 60 participants); however, the evidence was less conclusive at 12 months (RR 1.12, 95% CI 0.92 to 1.37; 2 studies; 195 participants; low certainty evidence). Investigators of one study reported improvement in visual acuity, but we could not estimate the effect of adjunctive steroid therapy because the study investigators did not provide any estimates of precision. Only one study examined intraocular pressure (IOP). The evidence suggests that adjunctive dexamethasone may reduce IOP slightly after 12 months of interventions (mean difference -1.90, 95% CI -3.78 to 0.07; 1 study; 167 participants; low certainty evidence). Three studies reported adverse events (retinal detachment, hypotony, proliferative vitreoretinopathy, seclusion of pupil, floaters, and pucker). The total numbers of adverse events were 14 out of 111 (12.6%) for those who received dexamethasone versus 12 out of 116 (10.3%) for those who did not. We could only perform a pooled analysis for the occurrence of retinal detachment: any difference between the two treatment groups was uncertain (RR 1.41, 95% CI 0.53 to 3.74; 227 participants; low certainty evidence). No study reported cost-related outcomes. AUTHORS' CONCLUSIONS: The currently available evidence on the effectiveness of adjunctive steroid therapy versus antibiotics alone in the management of acute endophthalmitis after intraocular surgery is inadequate. We found no studies that had enrolled cases of acute endophthalmitis following intravitreous injection. A combined analysis of two studies suggests that use of adjunctive steroids may provide a higher chance of having a good visual outcome at three months than not using adjunctive steroids. However, considering that most of the confidence intervals crossed the null, and that this review was limited in scope and applicability to clinical practice, it is not possible to conclude whether the use of adjunctive steroids is effective at this time. Any future trials should examine whether adjunctive steroids may be useful in certain clinical settings such as type of causative organism or etiology. These studies should include outcomes that take patients' symptoms and clinical examination into account; report outcomes in a uniform and consistent manner; and follow up at short- and long-term intervals.

Ophthalmic Immune-Related Adverse Events after Anti-CTLA-4 or PD-1 Therapy Recorded in the American Academy of Ophthalmology Intelligent Research in Sight Registry.

PURPOSE: Detailed study of ophthalmic immune-related adverse events (AEs), including determination of incidence and recurrence rates, is of integral importance in cancer immunotherapy to inform management and treatment guidelines. DESIGN: Retrospective registry study. PARTICIPANTS: Patients newly diagnosed with ophthalmic immune-related AEs between January 1, 2013, and December 31, 2017, in the American Academy of Ophthalmology's Intelligent Research in Sight (IRIS®) Registry. METHODS: Data were collected from electronic health records of IRIS® Registry participating ophthalmology practices. Patients with select ophthalmic immune-related AEs were identified by International Classification of Diseases diagnosis codes. The primary exposure of interest was prior initiation of immune checkpoint inhibitors (ICIs). MAIN OUTCOME MEASURES: Incidence of ophthalmic immune-related AEs within 1 year after initiation of ICI therapy was determined. Incidence rate ratios (IRRs) were derived by comparing incidence of ophthalmic immune-related AEs after ICIs versus rates of the same ocular complications in patients not taking ICIs in the entire registry population. Rates of ophthalmic immune-related AEs in patients with a past history of ocular inflammation or other specific ophthalmic condition before initiation of ICIs were examined further. RESULTS: A total of 3123 patients who received anti-CTLA-4 or anti-programmed cell death 1 (PD-1) therapy were identified, 112 of whom demonstrated an ophthalmic immune-related AE. Incidence rates for anterior uveitis, the most common ophthalmic immune-related AE, were 8209 per 100 000 for ipilimumab (anti-CTLA-4), 2542 per 100 000 for nivolumab (anti-PD-1), 2451 per 100 000 for pembrolizumab (anti-PD-1), 5556 per 100 000 for ipilimumab plus nivolumab, and 3740 per 100 000 among all ICIs. Rates of ophthalmic immune-related AEs among patients receiving ICI therapy were higher compared with baseline rates in the general registry population (anterior uveitis IRR, 13.9; other uveitis IRR, 43.0; papilledema IRR, 38.3). Patients with a history of uveitis or other ocular inflammatory condition demonstrated high recurrence rates of ophthalmic immune-related AEs after initiating ICIs (up to 51.1%). CONCLUSIONS: For patients initiating ICI therapy, early coordination with ophthalmic subspecialist care is important because rates of ophthalmic immune-related AEs are elevated compared with ocular complication rates in the entire registry population and patients with a history of prior autoimmune ocular disease are at high risk of recurrence of ocular complications.

Longitudinal Macular Structure-Function Relationships in Glaucoma.

PURPOSE: To investigate the relationship between longitudinal changes in macular thickness measurements from OCT and changes in central visual field (VF) in patients with glaucoma with central or advanced damage at baseline. DESIGN: Longitudinal cohort study. PARTICIPANTS: A total of 116 eyes with ≥3 years of follow-up and ≥5 macular OCT images and central 10° VF tests were selected. METHODS: OCT superpixels and VF locations were matched correcting for retinal ganglion cell (RGC) displacement. Superpixel thickness and VF total deviation (TD) values, in both logarithmic and linear scales, were averaged within 3 eccentricities (3.4°, 5.6°, and 6.8°) and superior and inferior hemiretinas and hemifields. We estimated pointwise TD rates of change and rates of change at superpixels for full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell inner plexiform layer (GCIPL), and ganglion cell layer (GCL). Correlation of structure-function (SF) rates of change was investigated with parametric tests. We compared the proportion of worsening and positive slopes for superpixels and VF test locations (negative vs. positive rates of change with P < 0.05) throughout the follow-up period. Permutation analyses were used to control specificity. MAIN OUTCOME MEASURES: Magnitude of correlation between structural and functional rates of change and proportion of worsening and positive slopes as a function of follow-up time. RESULTS: The median (interquartile range) follow-up and number of exams were 4.2 (3.7-4.6) years and 8 (7-9), respectively. The highest correlation of change rates was observed at 3.4° and 5.6° eccentricities (r = 0.24, 0.41, 0.40, and 0.40 for FMT, GCC, GCIPL, and GCL for 3.4° eccentricity and r = 0.28, 0.32, 0.31, and 0.32 for FMT, GCC, GCIPL, and GCL for 5.6° eccentricity, respectively). Although GCC measures demonstrated the highest overall longitudinal SF correlations, the differences were not statistically significant. Significant structural worsening was more frequently detected than functional deterioration at 3- and 5-year time points (P < 0.025). Permutation analyses also confirmed this finding. CONCLUSIONS: Correlations between central structural and functional rates of change were weak to fair in this cohort. Structural changes were detected more frequently than functional changes. Measurements of both structure and function are required for optimal detection of central progression.

Cyclodestructive procedures for refractory glaucoma.

BACKGROUND: Cyclodestructive procedures are often used in patients with refractory glaucoma who have failed to achieve lower intraocular pressure (IOP) from filtration procedures and maximal medical therapy. Destruction of the ciliary body helps to lower IOP by reducing aqueous humor formation. Of the many types of cyclodestructive procedures, laser cyclophotocoagulation (CPC) has become the most common surgical method for reducing aqueous inflow. Options for CPC are wide-ranging: they can be performed using a neodymium:yttrium-aluminum-garnet (Nd:YAG) or diode laser and laser energy can be delivered by either the contact or non-contact method. Another cyclodestructive procedure is endoscopic cyclophotocoagulation (ECP), which the ophthalmologist can use selectively to target the ciliary epithelium and ablate ciliary body tissue. There is debate regarding which cyclodestructive method is best and how they compare to other glaucoma surgeries. OBJECTIVES: To assess the relative effectiveness and safety of cyclodestructive procedures compared with other procedures in people with refractory glaucoma of any type and to assess the relative effectiveness and safety of individual cyclodestructive procedures compared with each other. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 9); Ovid MEDLINE; Embase.com; PubMed; LILACS BIREME; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 21 September 2018. SELECTION CRITERIA: We included randomized controlled trials or quasi-randomized trials in which participants underwent a secondary procedure for refractory glaucoma. We included trials with any laser type, route of administration, and laser settings. The primary comparison was any cyclodestructive procedure versus another glaucoma treatment, and the secondary comparisons were individual cyclodestructive procedures versus another cyclodestructive procedure. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the titles and abstracts from the database searches, and after retrieving the full-text reports of those that were potentially relevant, classified the full-text articles as included or excluded. Two review authors independently extracted data from the included studies and assessed the risk of bias. Discrepancies were resolved by discussion or by consultation with a third review author when necessary. MAIN RESULTS: We included five trials reporting data for 330 eyes (326 participants). One study to had a low risk of bias for most domains and the other studies had an overall unclear risk of bias. This review includes four different comparisons: 1) ECP versus Ahmed implant, 2) micropulse CPC versus continuous-wave CPC; 3) CPC with a diode versus Nd:YAG laser; and 4) CPC with an Nd:YAG laser emitting 8J versus 4J.No study reported data for our primary outcome, change from baseline in pain severity as reported by the participant or change in number of pain medications.For our primary comparison, we included one trial that compared ECP with the Ahmed implant. At 12-month follow-up, the mean difference (MD) in IOPs between groups was -1.14 mmHg (95% confidence interval (CI) -4.21 to 1.93; 58 participants; low-certainty evidence (LCE)). At 24 months postintervention, we found very LCE suggesting that visual acuity may be better among participants in the ECP group than in the Ahmed implant group (MD -0.24 logMAR, 95% CI -0.52 to 0.04; 54 participants), and the difference in the mean number of glaucoma medications used by participants in each group was unclear (MD -0.50, 95% CI -1.17 to 0.17; 54 participants; very LCE). Reported adverse events in the ECP group (34 participants) were one case each of hypotony, phthisis bulbi, retinal detachment, and choroidal detachment; in the Ahmed implant group (34 participants) there was one case of endophthalmitis, two cases of retinal detachment, and six cases of choroidal detachment.Three types of comparisons from four included studies provided data for our secondary comparisons. In the study that compared micropulse with continuous-wave CPC, median IOP was reported to be similar between the two groups at all time points. At 18 months postintervention, the median number of IOP-lowering medications was reduced from two to one in both groups. One participant in the micropulse and two in the continuous group exhibited worsened visual acuity. One case of prolonged inflammation was seen in the micropulse group (23 participants). Seven cases of prolonged inflammation, five cases of hypotony, and one case of phthisis bulbi were seen in the continuous group (23 participants).Two studies compared CPC using a semiconductor diode versus an Nd:YAG laser. At 12 months postintervention, the MD in IOP was 1.02 mmHg (95% CI -1.49 to 3.53) in one study (LCE). The second study did not report mean IOP beyond three months of follow-up. Neither study reported the mean change in best-corrected visual acuity or number of glaucoma medications. Both studies reported hypotony as an adverse event in three participants in each study.One study compared different energy settings of the same Nd:YAG laser. At 12-month follow-up, visual acuity was unchanged or improved in 21 of 33 participants in the 8J group and 20 of 27 participants in the 4J group (risk ratio 0.86, 95% CI 0.61 to 1.21; very LCE). More participants in the 8J group reduced the number of medications taken compared with the 4J group (RR 1.49, 95% CI 0.76 to 2.91; 50 participants; very low-certainty evidence). The presence of fibrin or hyphema were seen in five participants who received 8J and none who received 4J. There was a severe anterior chamber reaction in 11 of 26 (42%) participants who received 8J of energy and 2 of 21 (10%) participants who received 4J of energy. AUTHORS' CONCLUSIONS: Evidence from five studies included in this review was inconclusive as to whether cyclodestructive procedures for refractory glaucoma result in better outcomes and fewer complications than other glaucoma treatments, and whether one type of cyclodestructive procedure is better than another. The most commonly reported adverse events across all five studies were hypotony and phthisis bulbi. Large, well-designed randomized controlled trials are needed. Patient-reported outcomes such as pain and quality of life should be considered as primary outcomes or important secondary outcomes of future trials.

Risk Factors and Long-Term Outcomes in Patients with Low Intraocular Pressure after Trabeculectomy.

PURPOSE: To examine risk factors for low intraocular pressure (IOP) after trabeculectomy and to describe long-term outcomes in these eyes. DESIGN: Retrospective case-control study. PARTICIPANTS: Cases with low IOP included all patients with IOP ≤5 mmHg on 3 or more consecutive visits 3 months or later after trabeculectomy. Control patients without low IOP after trabeculectomy were randomly selected at a 1:2 case-to-control ratio. METHODS: A case-control study was performed of patients undergoing trabeculectomy at the Stein Eye Institute. Covariates included demographics, history of cataract surgery, refractive error, number of glaucoma medications, family history of glaucoma, diabetes, hypertension, visual acuity (VA), IOP, number of sutures in the scleral flap, laser suture lysis, surgeon, and laterality of surgery. Logistic regression modeling was used to examine associations between each covariate and low IOP. Postoperative outcomes that were examined included reoperation, vision loss, and surgical failure. The time between trabeculectomy and each outcome was compared between cases and controls with Cox proportional hazards regression modeling. MAIN OUTCOME MEASURES: Low IOP after trabeculectomy, reoperation, vision loss, and surgical failure. RESULTS: Of 3659 total trabeculectomies performed by 5 surgeons between 1990 and 2013, 64 eyes had low IOP (1.7%), which were compared with 130 control eyes. Fifteen of the 64 eyes with low IOP had hypotony maculopathy (23.4%). After accounting for differences in baseline IOP, laser suture lysis was negatively correlated with low IOP after trabeculectomy (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.13-0.87); surgeon was correlated with high vs. low IOP after trabeculectomy (OR, 5.32; 95% CI, 1.53-18.52). There were no statistically significant associations between low IOP and time to reoperation (hazard ratio [HR], 0.73; 95% CI, 0.32-1.68), vision loss (HR, 1.77; 95% CI, 0.81-3.88) or surgical failure (HR, 1.14; 95% CI, 0.62-2.11). In patients with low IOP, there was a higher unadjusted incidence of bleb revision in patients who had maculopathy (7.6 vs. 1.9 revisions/100 person-years; for maculopathy versus no maculopathy P = 0.008). CONCLUSIONS: The absence of laser suture lysis and surgeon are factors potentially associated with low IOP after trabeculectomy. Numeric hypotony does not necessarily represent clinical failure after trabeculectomy.

Aqueous shunts for glaucoma.

BACKGROUND: Aqueous shunts are employed to control intraocular pressure (IOP) for people with primary or secondary glaucomas who fail or are not candidates for standard surgery. OBJECTIVES: To assess the effectiveness and safety of aqueous shunts for reducing IOP in glaucoma compared with standard surgery, another type of aqueous shunt, or modification to the aqueous shunt procedure. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 8), MEDLINE Ovid (1946 to August 2016), Embase.com (1947 to August 2016), PubMed (1948 to August 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to August 2016), ClinicalTrials.gov (www.clinicaltrials.gov); searched 15 August 2016, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 15 August 2016. We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 15 August 2016. We also searched the reference lists of identified trial reports and the Science Citation Index to find additional trials. SELECTION CRITERIA: We included randomized controlled trials that compared various types of aqueous shunts with standard surgery or to each other in eyes with glaucoma. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results for eligibility, assessed the risk of bias, and extracted data from included trials. We contacted trial investigators when data were unclear or not reported. We graded the certainty of the evidence using the GRADE approach. We followed standard methods as recommended by Cochrane. MAIN RESULTS: We included 27 trials with a total of 2099 participants with mixed diagnoses and comparisons of interventions. Seventeen studies reported adequate methods of randomization, and seven reported adequate allocation concealment. Data collection and follow-up times varied.Four trials compared an aqueous shunt (Ahmed or Baerveldt) with trabeculectomy, of which three reported one-year outcomes. At one-year, the difference in IOP between aqueous shunt groups and trabeculectomy groups was uncertain (mean difference (MD) 2.55 mmHg, 95% confidence interval (CI) -0.78 to 5.87; 380 participants; very low-certainty evidence). The difference in logMAR visual acuity was also uncertain (MD 0.12 units, 95% CI -0.07 to 0.31; 380 participants; very low-certainty evidence). In two trials, the difference in visual field score was uncertain (MD -0.25, 95% CI -1.91 to 1.40; 196 participants; very low-certainty evidence). The mean number of antiglaucoma medications was higher in the aqueous shunt group than the trabeculectomy group in one trial (MD 0.80, 95% CI 0.48 to 1.12; 184 participants; low-certainty evidence). The effect on needing additional glaucoma surgery was uncertain between groups in two trials (risk ratio (RR) 0.24, 95% CI 0.04 to 1.36; 329 participants; very low-certainty evidence). In one trial, fewer total adverse events were reported in the aqueous shunt group than the trabeculectomy group (RR 0.59, 95% CI 0.43 to 0.81; 212 participants; very low-certainty evidence). No trial reported quality-of-life outcomes at one-year follow-up.Two trials that compared the Ahmed implant with the Baerveldt implant for glaucoma found higher mean IOP in the Ahmed group at one-year follow-up (MD 2.60 mmHg, 95% CI 1.58 to 3.62; 464 participants; moderate-certainty evidence). The difference in logMAR visual acuity was uncertain between groups (MD -0.07 units, 95% CI -0.27 to 0.13; 501 participants; low-certainty evidence). The MD in number of antiglaucoma medications was within one between groups (MD 0.35, 95% CI 0.11 to 0.59; 464 participants; moderate-certainty evidence). More participants in the Ahmed group required additional glaucoma surgery than the Baerveldt group (RR 2.77, 95% CI 1.02 to 7.54; 514 participants; moderate-certainty evidence). The two trials reported specific adverse events but not overall number of adverse events. Neither trial reported visual field or quality-of-life outcomes at one-year follow-up.One trial compared the Ahmed implant with the Molteno implant for glaucoma over two-year follow-up. Mean IOP was higher in the Ahmed group than the Molteno group (MD 1.64 mmHg, 95% CI 0.85 to 2.43; 57 participants; low-certainty evidence). The differences in logMAR visual acuity (MD 0.08 units, 95% CI -0.24 to 0.40; 57 participants; very low-certainty evidence) and mean deviation in visual field (MD -0.18 dB, 95% CI -3.13 to 2.77; 57 participants; very low-certainty evidence) were uncertain between groups. The mean number of antiglaucoma medications was also uncertain between groups (MD -0.38, 95% CI -1.03 to 0.27; 57 participants; low-certainty evidence). The trial did not report the proportion needing additional glaucoma surgery, total adverse events, or quality-of-life outcomes.Two trials compared the double-plate Molteno implant with the Schocket shunt for glaucoma; one trial reported outcomes only at six-month follow-up, and the other did not specify the follow-up time. At six-months, mean IOP was lower in the Molteno group than the Schocket group (MD -2.50 mmHg, 95% CI -4.60 to -0.40; 115 participants; low-certainty evidence). Neither trial reported the proportion needing additional glaucoma surgery, total adverse events, or visual acuity, visual field, or quality-of-life outcomes.The remaining 18 trials evaluated modifications to aqueous shunts, including 14 trials of Ahmed implants (early aqueous suppression versus standard medication regimen, 2 trials; anti-vascular endothelial growth factor agent versus none, 4 trials; corticosteroids versus none, 2 trials; shunt augmentation versus none, 3 trials; partial tube ligation versus none, 1 trial; pars plana implantation versus conventional implantation, 1 trial; and model M4 versus model S2,1 trial); 1 trial of 500 mm2 Baerveldt versus 350 mm2 Baerveldt; and 3 trials of Molteno implants (single-plate with oral corticosteroids versus single-plate without oral corticosteroids, 1 trial; double-plate versus single-plate, 1 trial; and pressure-ridge versus double-plate with tube ligation, 1 trial). AUTHORS' CONCLUSIONS: Information was insufficient to conclude whether there are differences between aqueous shunts and trabeculectomy for glaucoma treatment. While the Baerveldt implant may lower IOP more than the Ahmed implant, the evidence was of moderate-certainty and it is unclear whether the difference in IOP reduction is clinically significant. Overall, methodology and data quality among existing randomized controlled trials of aqueous shunts was heterogeneous across studies, and there are no well-justified or widely accepted generalizations about the superiority of one surgical procedure or device over another.

Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis after intraocular procedure.

BACKGROUND: Endophthalmitis refers to severe infection within the eye that involves the aqueous humor or vitreous humor, or both, and threatens vision. Most cases of endophthalmitis are exogenous (i.e. due to inoculation of organisms from an outside source), and most exogenous endophthalmitis is acute and occurs after an intraocular procedure. The mainstay of treatment is emergent administration of broad-spectrum intravitreous antibiotics. Due to their anti-inflammatory effects, steroids in conjunction with antibiotics have been proposed to be beneficial in endophthalmitis management. OBJECTIVES: To assess the effects of antibiotics combined with steroids versus antibiotics alone for the treatment of acute endophthalmitis following intraocular surgery or intravitreous injection. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), MEDLINE Ovid (1946 to 8 December 2016), Embase Ovid (1980 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 8 December 2016, ClinicalTrials.gov (www.clinicaltrials.gov); searched 8 December 2016, and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 8 December 2016. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included randomized controlled trials comparing the effectiveness of adjunctive steroids with antibiotics alone in the management of acute, clinically diagnosed endophthalmitis following intraocular surgery or intravitreous injection. We excluded trials with participants with endogenous endophthalmitis unless outcomes were reported by source of infection. We imposed no restrictions on the method or order of administration, dose, frequency, or duration of antibiotics and steroids. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed risk of bias, and extracted data using methods expected by Cochrane. We contacted study authors to try to obtain missing information or information to clarify risk of bias. We conducted a meta-analysis for any outcomes that were reported by at least two studies. Outcomes reported from single studies were summarized in the text. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included three trials with a total of 95 randomized participants in this review and identified one ongoing trial. The studies were conducted in South Africa, India, and the Netherlands. Out of the 92 analyzed participants, 91 participants were diagnosed with endophthalmitis following cataract surgery. In the remaining participant, endophthalmitis was attributable to penetrating keratoplasty. All studies used intravitreous dexamethasone for adjunctive steroid therapy and a combination of two intravitreous antibiotics that provided gram-positive and gram-negative coverage for the antibiotic therapy. We judged one trial to be at overall low risk of bias and two studies to be at overall unclear risk of bias due to lack of reporting of study methods. None of the three trials had been registered in a clinical trial register.While none of the included studies reported the primary outcome of complete resolution of endophthalmitis as defined in our protocol, one study reported combined anatomical and functional success (i.e. proportion of participants with intraocular pressure of at least 5 mmHg and visual acuity of at least 6/120). Very low-certainty evidence suggested no difference in combined success when comparing adjunctive steroid antibiotics alone (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.80 to 1.45; 32 participants). Low-certainty evidence from two studies showed that a higher proportion of participants who received adjunctive dexamethasone had a good visual outcome (Snellen visual acuity 6/6 to 6/18) at three months compared with those in the antibiotics-alone group (RR 1.95, 95% CI 1.05 to 3.60; 60 participants). Similarly, low-certainty evidence from one study suggested that more participants in the dexamethasone group had a good visual outcome at 12 months compared to those who did not receive dexamethasone (RR 2.00, 95% CI 0.98 to 4.08; 28 participants). Investigators of one study reported improvement in visual acuity, but we could not estimate the effect of adjunctive steroid therapy because the study investigators did not provide standard deviations or standard errors. Two studies reported adverse events (retinal detachment, hypotony, proliferative vitreoretinopathy, and seclusion of pupil). The total numbers of adverse events were 8 out of 30 (26.7%) for those who received dexamethasone versus 6 out of 30 (20.0%) for those who did not. We could only perform a pooled analysis for the occurrence of retinal detachment; any difference between the two treatment groups was uncertain (RR 1.57, 95% CI 0.50 to 4.90; 60 participants) (very low-certainty evidence). No study reported intraocular pressure or cost outcomes. AUTHORS' CONCLUSIONS: Current evidence on the effectiveness of adjunctive steroid therapy versus antibiotics alone in the management of acute endophthalmitis after intraocular surgery is inadequate. We found no studies that had enrolled cases of acute endophthalmitis following intravitreous injection. A combined analysis of two studies suggests adjunctive steroids may provide a higher probability of having a good visual outcome at three months than not using adjunctive steroids. However, considering that most of the confidence intervals crossed the null and that this review was limited in scope and applicability to clinical practice, it is not possible to conclude whether the use adjunctive steroids is effective at this time. Any future trials should examine whether adjunctive steroids may be useful in certain clinical settings such as type of causative organism or etiology. These studies should include outcomes that take patient's symptoms and clinical examination into account, report outcomes in a uniform and consistent manner, and follow up at short- and long-term intervals.

Surgical interventions for vertical strabismus in superior oblique palsy.

BACKGROUND: Superior oblique palsy is a common cause of vertical strabismus in adults and children. Patients may be symptomatic from binocular vertical diplopia or compensatory head tilt required to maintain single vision. Most patients who are symptomatic elect to undergo strabismus surgery, but the optimal surgical treatment for vertical strabismus in people with superior oblique palsy is unknown. OBJECTIVES: To assess the relative effects of surgical treatments compared with another surgical intervention, non-surgical intervention, or observation for vertical strabismus in people with superior oblique palsy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 13 December 2016), Embase Ovid (1947 to 13 December 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 13 December 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 13 December 2016, ClinicalTrials.gov (www.clinicaltrials.gov); searched 13 December 2016, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 13 December 2016. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included randomized trials that compared at least one type of surgical intervention to another surgical or non-surgical intervention or observation. DATA COLLECTION AND ANALYSIS: Two review authors independently completed eligibility screening, data abstraction, 'Risk of bias' assessment, and grading of the evidence. MAIN RESULTS: We identified two randomized trials comparing four different surgical treatments for this condition, two methods in each trial. The studies included a total of 45 children and adults. The surgical treatments were all procedures to weaken the ipsilateral inferior oblique muscle. One study compared inferior oblique myectomy to recession of 10 mm; the other study compared inferior oblique disinsertion to anterior transposition (2 mm anterior to the temporal border of the inferior rectus insertion).We judged both studies to be at unclear risk of bias due to incomplete reporting of methods and other methodological deficiencies.Neither study reported data on the primary outcome of this review, which was the proportion of participants with postoperative surgical success, defined as hypertropia less than 3 prism diopters (PD) in primary gaze. However, both studies reported the average reduction in hypertropia in primary gaze. One study found that at 12 months' postoperatively the average decrease in hypertropia was higher in participants who underwent inferior oblique myectomy than in those who underwent recession, however data were not available for statistical comparison. The other trial found that after at least six months of follow-up, the mean decrease in primary position hypertropia was lower in participants who underwent inferior oblique disinsertion than in those who underwent anterior transposition (mean difference (MD) -5.20 PD, 95% confidence interval (CI) -7.76 to -2.64; moderate-quality evidence).Both trials also reported the average postoperative reduction in vertical deviation in adduction. One study reported that the average reduction in hypertropia in adduction was greater in participants who underwent inferior oblique myectomy than in those who underwent recession, but data were not available for statistical comparison. The other study found a lower decrease in hypertropia in contralateral gaze in participants who underwent inferior oblique disinsertion than in those who underwent anterior transposition (MD -7.10 PD, 95% CI -13.85 to -0.35; moderate-quality evidence).Secondary outcomes with sufficient data for analysis included proportion of participants with preoperative head tilt that resolved postoperatively and proportion of participants who underwent a second surgery. These outcomes were assessed in the trial comparing inferior oblique anterior transposition to disinsertion; both outcomes favored anterior transposition (risk ratio 7.00, 95% CI 0.40 to 121.39 for both outcomes; very low-quality evidence). None of the participants who underwent inferior oblique anterior transposition or disinsertion developed postoperative hypotropia or reversal of the vertical deviation. All participants who underwent inferior oblique anterior transposition developed elevation deficiency, which the authors deemed to be clinically insignificant in all cases, whereas no participants who underwent inferior oblique disinsertion experienced this complication. Additionally, the trial comparing inferior oblique myectomy to recession reported that no participant in either group required another strabismus surgery during the postoperative period. AUTHORS' CONCLUSIONS: The two trials included in this review evaluated four inferior oblique weakening procedures for surgical treatment of superior oblique palsy. We found no trials comparing other types of surgical procedures for this disorder. Both studies had enrolled a small number of participants and provided low-quality evidence due to limitations in completeness and applicability. We therefore found no high-quality evidence to support recommendations for optimal surgical treatment of superior oblique palsy. Rigorously designed, conducted, and reported randomized trials are needed to identify the optimal surgical treatment for vertical strabismus in this disorder.

Network Meta-analysis for Clinical Practice Guidelines: A Case Study on First-Line Medical Therapies for Primary Open-Angle Glaucoma.

BACKGROUND: Network meta-analysis compares multiple treatment options for the same condition and may be useful for developing clinical practice guidelines. PURPOSE: To compare treatment recommendations for first-line medical therapy for primary open angle-glaucoma (POAG) from major updates of American Academy of Ophthalmology (AAO) guidelines with the evidence available at the time, using network meta-analysis. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were searched on 11 March 2014 for randomized, controlled trials (RCTs) of glaucoma monotherapies compared with placebo, vehicle, or no treatment or other monotherapies. The AAO Web site was searched in August 2014 to identify AAO POAG guidelines. STUDY SELECTION: Eligible RCTs were selected by 2 independent reviewers, and guidelines were selected by 1 person. DATA EXTRACTION: One person abstracted recommendations from guidelines and a second person verified. Two people independently abstracted data from included RCTs. DATA SYNTHESIS: Guidelines were grouped together on the basis of literature search dates, and RCTs that existed at 1991, 1995, 1999, 2004, and 2009 were analyzed. The outcome of interest was intraocular pressure (IOP) at 3 months. Only the latest guideline made a specific recommendation: prostaglandins. Network meta-analyses showed that all treatments were superior to placebo in decreasing IOP at 3 months. The mean reductions (95% credible intervals [CrIs]) for the highest-ranking class compared with placebo were as follows: 1991: ß-blockers, 4.01 (CrI, 0.48 to 7.43); 1995: α2-adrenergic agonists, 5.64 (CrI, 1.73 to 9.50); 1999: prostaglandins, 5.43 (CrI, 3.38 to 7.38); 2004: prostaglandins, 4.75 (CrI, 3.11 to 6.44); 2009: prostaglandins, 4.58 (CrI, 2.94 to 6.24). LIMITATION: When comparisons are informed by a small number of studies, the treatment effects and rankings may not be stable. CONCLUSION: For timely recommendations when multiple treatment options are available, guidelines developers should consider network meta-analysis. PRIMARY FUNDING SOURCE: National Eye Institute, National Institutes of Health.

Cataract Surgery and Mortality in the United States Medicare Population.

PURPOSE: To determine the association between cataract surgery and all-cause mortality in United States Medicare patients with cataract. DESIGN: Retrospective cohort study. PARTICIPANTS: A 5% random sample of United States Medicare beneficiaries with a diagnosis of cataract from the 2002 through 2012 Denominator and Physician/Supplier Part B files. METHODS: The exposure of interest was cataract surgery and the outcome of interest was all-cause mortality. Baseline characteristics that were examined included demographics, systemic comorbidities, and ocular comorbidities. Cox proportional hazards regression modeling was used to assess the association between cataract surgery and mortality. Additional subgroup analyses were performed in propensity score deciles and within strata of age, gender, region, systemic disease burden, and in patients with versus without severe cataract subtypes. MAIN OUTCOME MEASURES: All-cause mortality. RESULTS: The 5% Medicare sample included 1 501 420 patients with cataract, of whom 544 984 (36.3%) underwent cataract surgery. Patients with cataract surgery were followed up for a mean of 11.4 quarters (standard deviation [SD], 10.8 quarters; range, 0.0-44.0 quarters), whereas patients without cataract surgery were followed up for a mean of 12.9 quarters (SD, 12.2 quarters; range, 0.0-44.0 quarters). Mortality incidence was 2.78 deaths per 100 person-years in patients with cataract surgery and 2.98 deaths per 100 person-years in patients without surgery (P < 0.0001). Overall, patients with cataract surgery had a lower adjusted hazard of mortality compared with patients without surgery (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.72-0.74). The strongest associations were observed in patients with a high propensity score decile (HR, 0.52; 95% CI, 0.50-0.54), patients 80 to 84 years of age (HR, 0.63; 95% CI, 0.62-0.65), women (HR, 0.69; 95% CI, 0.68-0.70), patients in the western United States (HR, 0.52; 95% CI, 0.32-0.86), patients with a moderate systemic disease burden (HR, 0.71; 95% CI, 0.69-0.72), and patients with severe cataract (HR, 0.68; 95% CI, 0.66-0.70). CONCLUSIONS: In a national cohort of United States Medicare beneficiaries with cataract, cataract surgery was associated with decreased all-cause mortality. Further studies are needed to examine mechanisms surrounding the association between cataract surgery and mortality.

Prostaglandin Eyedrops Are Associated With Decreased Thicknesses of Eyelid Dermis and Orbicularis Oculi Muscle: Ultrasonographic Findings.

PURPOSE: To investigate the effect of prostaglandin analog eyedrops on the periorbital soft tissue using high-resolution ultrasonography. METHODS: In this cross-sectional study, the authors included patients with bilateral glaucoma on unilateral prostaglandin therapy for the past 12 or more contiguous months. High-resolution ultrasonography was performed bilaterally on the upper and lower eyelids of each subject to measure thicknesses of dermis, orbicularis oculi muscle, and skin to arcus marginalis distance. Comparisons were made between eyes on prostaglandin eyedrops versus those not on prostaglandin analogs. RESULTS: Twenty patients (16 females, 4 males) with a mean age of 67.2 ± 6.4 years were recruited. The mean duration of prostaglandin analog therapy was 5.4 ± 3.9 years. The authors found that eyes on prostaglandin analog therapy had statistically significantly reduced thicknesses of dermis, orbicularis oculi muscle, and skin to arcus marginalis distance in the upper and lower eyelids compared with the fellow eyes (p < 0.05 for all). In univariate regression analysis, the amount of changes in thicknesses of dermis, orbicularis oculi muscle, and skin to arcus marginalis distance among eyes on prostaglandin analog therapy and the fellow eyes was not statistically significantly associated with different variables including age, gender, years of being on prostaglandin analog therapy, type of prostaglandin analog, history of glaucoma and/or cataract surgeries, intraocular pressure, and number of glaucoma medications. CONCLUSIONS: The findings indicate that eyes on prostaglandin analog therapy have reduced thicknesses of dermis, orbicularis oculi muscle, and skin to arcus marginalis distance compared with the fellow eyes.

Use of health care claims data to study patients with ophthalmologic conditions.

OBJECTIVE: To describe what information is or is not included in health care claims data, provide an overview of the main advantages and limitations of performing analyses using health care claims data, and offer general guidance on how to report and interpret findings of ophthalmology-related claims data analyses. DESIGN: Systematic review. PARTICIPANTS: Not applicable. METHODS: A literature review and synthesis of methods for claims-based data analyses. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Some advantages of using claims data for analyses include large, diverse sample sizes, longitudinal follow-up, lack of selection bias, and potential for complex, multivariable modeling. The disadvantages include (a) the inherent limitations of claims data, such as incomplete, inaccurate, or missing data, or the lack of specific billing codes for some conditions; and (b) the inability, in some circumstances, to adequately evaluate the appropriateness of care. In general, reports of claims data analyses should include clear descriptions of the following methodological elements: the data source, the inclusion and exclusion criteria, the specific billing codes used, and the potential confounding factors incorporated in the multivariable models. CONCLUSIONS: The use of claims data for research is expected to increase with the enhanced availability of data from Medicare and other sources. The use of claims data to evaluate resource use and efficiency and to determine the basis for supplementary payment methods for physicians is anticipated. Thus, it will be increasingly important for eye care providers to use accurate and descriptive codes for billing. Adherence to general guidance on the reporting of claims data analyses, as outlined in this article, is important to enhance the credibility and applicability of findings. Guidance on optimal ways to conduct and report ophthalmology-related investigations using claims data will likely continue to evolve as health services researchers refine the metrics to analyze large administrative data sets.

Acute angle closure: qualitative and quantitative evaluation of the anterior segment using anterior segment optical coherence tomography.

BACKGROUND: To evaluate different mechanisms of acute angle closure and to compare it with unaffected fellow eyes and primary angle closure suspects using anterior segment optical coherence tomography. DESIGN: Prospective, cross-sectional. PARTICIPANTS: 116 eyes (76 patients) with angle closure disease were included. METHODS: Eyes were categorized into three groups: (i) acute angle closure (40 eyes); (ii) fellow eyes of acute angle closure (40 eyes); and (iii) primary angle closure suspect (36 eyes). Complete ophthalmic examinations including gonioscopy, A-scan biometry and anterior segment optical coherence tomography were performed. MAIN OUTCOME MEASURE: Based on the anterior segment optical coherence tomography images, four mechanisms of primary angle closure including pupil block, plateau iris configuration, thick peripheral iris roll and exaggerated lens vault were evaluated among the three subtypes of angle closure disease. RESULTS: There was a statistically significant difference in the mechanism of angle closure disease among the three groups (P < 0.001). Although the majority of fellow and primary angle closure suspect eyes had pupil block mechanism (77.5% and 75%, respectively), only 37.5% of acute angle closure eyes had dominant pupil block mechanism. The percentage because of exaggerated lens vault was greatest in acute angle closure eyes (50%). Acute angle closure eyes had the shallowest anterior chamber depth (P < 0.001), least iris curvature (P < 0.001) and greatest lens vault (P = 0.003) compared with the other two groups. CONCLUSIONS: A statistically significant difference in the underlying primary angle closure mechanisms among acute angle closure eyes as compared with their fellow eyes and primary angle closure suspect may exist.