Patient-Reported Outcome Measure Use in Guidelines Published by the American Academy of Ophthalmology: A Review.

TOPIC: We reviewed the use of patient-reported outcome measures (PROMs) in the treatment of ophthalmologic conditions as recommended by the Clinical Practice Guidelines (CPGs) published by the American Academy of Ophthalmology (AAO). CLINICAL RELEVANCE: Patient-reported outcome measures are standardized instruments that provide information regarding a patient's health status or health-related quality of life. Patient-reported outcome measures are increasingly used to inform study end points in ophthalmology studies. However, the extent to which PROMs are ultimately informing patient management recommendations in ophthalmology as part of CPGs remains an area of evidence gap. METHODS: We included all CPGs published by the AAO from inception to June 2022. We also included all primary studies and systematic reviews cited in the treatment sections of the CPGs evaluating treatment of an ophthalmic condition. The primary outcome was the frequency of PROMs discussed in CPGs and in cited studies evaluating treatment. Secondary outcomes included frequency of minimal important difference (MID) use to contextualize PROM results and percentage of strong and discretionary recommendations supported by PROMs. We published a study protocol a priori on PROSPERO (CRD42022307427). Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We assessed risk of bias using the Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. RESULTS: We identified 24 eligible CPGs, providing 2458 cited studies (2191 primary, 267 secondary) evaluating treatment of eye conditions. Ten CPGs (41.7%) reported consideration of PROMs. Of these, 31 of 94 (33%) recommendations were informed by studies evaluating a PROM as an outcome. Across all studies cited in the development of CPGs, 221 (9.0%) used PROMs as a primary or secondary outcome, of which 4 PROM results (1.8%) were interpreted using an empirically determined MID. Overall, the risk of bias was low for all CPGs. CONCLUSIONS: Overall, outcomes of PROMs are seldom used in ophthalmology CPGs published by the AAO and in cited primary and secondary research on treatments. When PROMs were considered, their interpretation was seldom based on an MID. To improve patient care, guideline developers may consider incorporating PROMs and applicable MIDs to inform key outcomes when formulating treatment recommendations. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Missed appointments in a tertiary academic pediatric ophthalmology and adult strabismus service: cross-sectional study and literature review.

PURPOSE: To investigate the rate of missed appointments in a Canadian academic hospital-based pediatric ophthalmology and adult strabismus practice and the demographic and clinical factors associated with missed appointments. METHODS: This cross-sectional study included all consecutive patients seen from June 1, 2018, to May 31, 2019. Multivariable logistic regression model assessed associations between clinical and demographic variables with no-show status. A literature review on evidence-based interventions to reduce no-show appointments in ophthalmology was performed. RESULTS: Of 3,922 visits, 718 (18.3%) were no-shows. Characteristics associated with no-shows included new patient (OR = 1.4; 95% CI, 1.1-1.7 [P = 0.001]), age 4-12 years (OR = 1.6; 95% CI, 1.1-2.3 [P = 0.011]) or age 13-18 years (OR = 1.8; 95% CI, 1.2-2.7 [P = 0.007]) compared with age 19+ years, history of previous no-shows (OR = 2.2; 95% CI, 1.8-2.7 [P = 0.001]), referrals from nurse practitioners (OR = 1.8; 95% CI, 1.0-3.2 [P = 0.037]), nonsurgical diagnoses such as retinopathy of prematurity (OR = 3.2; 95% CI, 1.8-5.6 [P < 0.001]), and winter season (OR = 1.4; 95% CI, 1.2-1.7 [P < 0.001]). CONCLUSIONS: Missed appointments in our pediatric ophthalmology and strabismus academic center are more likely new patient referrals, prior no-shows, referrals from nurse practitioners, and nonsurgical diagnoses. These findings may facilitate targeted strategies to help improve utilization of healthcare resources.

Prophylactic intraocular pressure lowering measures in anti-vascular endothelial growth factor therapy: A systematic review and meta-analysis.

Acute intraocular pressure (IOP) elevation following repeat intravitreal anti-vascular endothelial growth factor (VEGF) injections (IVI) may pose a risk to the integrity of the retinal nerve fiber (RNFL). This meta-analysis investigates the role of IOP-lowering interventions such as an anterior chamber paracentesis (ACP) and IOP-lowering medications on the IOP in patients undergoing IVIs. MEDLINE, EMBASE, and the Cochrane Library were searched up to February, 2021. Studies investigating IOP-lowering interventions in patients undergoing IVI versus controls were included. The primary outcome was the IOP in the short- and long-term post-IVI. Secondary outcomes were changes in the RNFL thickness and best corrected visual acuity (BCVA). ACP at time of anti-VEGF injection significantly lowered IOP immediately post anti-VEGF (WMD: -27.98 mm Hg, P < 0.001). Patients in the ACP group also had significantly thicker RNFL compared to control (WMD: 2.07 um, P < 0.00001) at median follow-up of 16.5 months. IOP-lowering medications (on the day of injection or in the long-term) significantly reduced IOP up to 30 minutes after injection (WMD: -3.31 mm Hg, P = 0.003). This effect was statistically significant between the 2 arms up to 1 month follow-up. There was no difference in BCVA in intervention versus controls. ACP reduces immediate IOP spikes post-IVI and preserves the RNFL in the short- and longterms IOP-lowering medications also reduce IOP spike, with limited data on RNFL thickness.

Comparison of Idiopathic Intracranial Hypertension Patients With and Without Anemia.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition of elevated intracranial pressure without an identifiable cause. It mostly affects young obese women but has been reported in individuals newly diagnosed with anemia or with chronic anemia. The relationship between anemia and IIH is not well elucidated. This study aims to characterize the course of IIH in anemic patients. METHODS: Consecutive patients with IIH were recruited from neuro-ophthalmology clinics. Subsequent retrospective chart review obtained information on symptoms, complete blood counts (CBCs), visual acuity, visual fields, and optic disc edema at baseline and follow-up. Anemia was diagnosed by hemoglobin <120 g/L (women) and <130 g/L (men). RESULTS: One hundred twenty-three patients with IIH were recruited for this study, and 22.8% (28/123) had anemia. More anemic individuals had mild-to-moderate visual acuity impairment (logarithm of minimum angle of resolution 0.3-1, P = 0.01) and worse automated mean deviation ( P = 0.048). The median follow-up time was 47.4 weeks (interquartile range:20.1-91.8). Fifteen of 28 patients with anemia received anemia treatment and showed a trend toward increased hemoglobin. At follow-up, there were no differences in the visual acuity, but patients with anemia had worse automated mean deviation on visual fields ( P = 0.045). CONCLUSIONS: IIH patients with anemia had worse visual function at presentation and worse final visual field parameters. This suggests that CBCs should be obtained for patients with papilledema because it may influence final visual outcome.

Anemia and Idiopathic Intracranial Hypertension: A Case-Control Study.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition that mostly affects obese women of childbearing age but has been reported to be temporally related to new diagnoses of anemia. Despite these reports, the association between anemia and IIH remains controversial. The present study aimed to understand the strength of association between anemia and IIH through a case-control design. METHODS: Consecutive IIH patients were recruited from neuro-ophthalmology clinics and matched by age and sex to consecutive patients attending neuro-ophthalmology clinics with diagnoses other than IIH. Complete blood counts (CBCs) were reviewed within 6 months of neuro-ophthalmology presentation, and anemia was diagnosed by hemoglobin of <120 g/L in women and <130 g/L in men. Anemia was classified as microcytic (mean corpuscular volume (MCV) < 80 fL), normocytic (MCV 80-100 fL), and macrocytic (MCV > 100 fL) as well as mild (hemoglobin >110 g/L), moderate (hemoglobin 80-109 g/L), and severe (hemoglobin <80 g/L). RESULTS: One hundred twenty-three IIH patients and 113 controls were included in the study. More IIH patients than controls had anemia (22.8%, 28/123 vs 10.6%, 12/113, P = 0.01) with an odds ratio of 2.48 (95% CI: 1.19, 5.16). There were no differences in severity of anemia or MCV between IIH patients and controls, with anemia most often being mild (57.1%, 16/28 vs 75%, 9/12) and normocytic (50.0%, 14/28 vs 50.0%, 6/12). However, 17.9% (5/28) of IIH patients had severe anemia compared with zero in the control group. IIH patients had a higher mean platelet count than controls ( P < 0.001), and there were no differences on leukocyte counts. CONCLUSION: Idiopathic intracranial hypertension patients have a higher prevalence of anemia compared with non-IIH neuro-ophthalmology patients. The anemia was mostly mild and may be explained by other factors related to worse health status and obesity, including low socioeconomic status, poor nutrition, and polycystic ovary syndrome. However, as a CBC is a widely available test and anemia may influence the IIH disease course, we propose that this test be obtained in all patients with new papilledema.

Treatment and prophylaxis of radiation optic neuropathy: A systematic review and meta-analysis.

PURPOSE: Radiation optic neuropathy (RON) generally follows radiation therapy that exceed 50 Gy to the visual axis and occurs within three years of therapy. Currently, there are no universally accepted treatments or prophylaxis for RON. The review aimed to examine the efficacy of all treatments and prophylaxis for RON. METHODS: MEDLINE, Embase, the Cochrane Library, and gray literature were searched to December 2020. Studies on treatment(s) and/or prophylaxis of RON were included. Results were meta-analyzed using a random-effects model. Primary outcomes included the proportions of patients who experienced improvement, no change, or worsening of visual acuity (VA) for each treatment. Secondary outcome was the incidence of RON for studies on prophylaxis. RESULTS: Overall, 50 studies (n = 5397) were included. Meta-analysis (n = 1752) showed significantly lower incidence of RON in patients who underwent intravitreal anti-VEGF prophylaxis compared to control (RR 0.64, 95%CI [0.48, 0.86]) for uveal melanoma. Intravitreal anti-VEGF injections (n = 68), hyperbaric oxygen therapy alone (n = 14), and pentoxifylline (n = 5) resulted in improved or stable vision ≤1 logMAR in 54.5%, 42.9%, and 40.0% of patients, respectively. Systemic corticosteroids (n = 82), anticoagulants (n = 12), and systemic bevacizumab (n = 7) showed improved or stable vision ≤1 logMAR in 17.1%, 33.3%, and 14.3% of patients, respectively. Overall risk of bias was low, but evidence was limited to retrospective studies. CONCLUSION: Intravitreal anti-VEGF injections reduced incidence of RON in irradiated uveal melanoma patients. Systemic corticosteroids, systemic bevacizumab, and warfarin alone are likely ineffective treatments. Early hyperbaric oxygen therapy and intravitreal anti-VEGF injections were most effective among those investigated and require further investigation.

Demographic Risk Factors of Retinopathy of Prematurity: A Systematic Review of Population-Based Studies.

INTRODUCTION: Current national guidelines use gestational age (GA) and birth weight (BW) as their basis for retinopathy of prematurity (ROP) screening. The strength of association of these and other demographic risk factors is inconsistent across studies. This review aims to evaluate the strength of association of documented risk factors for ROP in large sample, population-based studies. METHODS: MEDLINE, EMBASE, and Cochrane Library were searched from January 2010 to May 2020. Original studies reporting the risk of ROP in a region and demographic risk factors were included. RESULTS: Eighteen studies comprising 342,005 infants were included. The overall risk of ROP in preterm infants was 18.8%. For every week decrease in GA, there was a median adjusted odds ratio (aOR) of 1.4 times (range 1.2-1.9) of developing ROP. For every 100-g decrease in BW, the median aOR was 1.8 times (range 1.2-2.7). Higher risk was found in infants with neonatal sepsis and bronchopulmonary dysplasia. The risk of any, severe, and treatment-requiring ROP was highest for 23 weeks GA, which was 66.5, 40.3, and 39.4%, respectively. Regions with higher neonatal mortality rates had the highest mean GA of infants with ROP. CONCLUSION: For every week decrease in GA and every 100-g decrease in BW, there was a median of 1.4 times and 1.8 times the odds of developing ROP, respectively. Further research is required to clarify the role of additional risk factors.

Anemia and Idiopathic Intracranial Hypertension: A Systematic Review and Meta-analysis.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition typically affecting young, obese women. Although anemia is recognized as a risk factor of IIH from case reports, their relationship remains controversial as several comparative studies showed no significant association. This study aimed to examine the relationship between anemia and IIH. METHODS: MEDLINE, Embase, Cochrane Library, and grey literature were searched to September 2020. Primary studies on patients with diagnoses of anemia of any kind and IIH were included. Primary outcomes included the total number of cases of anemia and IIH. A meta-analysis on the prevalence of anemia in IIH compared with control patients was conducted. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to rate the quality of evidence. RESULTS: Overall, 62 cases and 5 observational or case-control studies were included. Pooled incidence of anemia in patients with IIH was 195/1,073 (18.2%). Patients with IIH (n = 774) had a significantly higher prevalence of anemia compared with controls (n = 230,981) (RR 1.44 [95% confidence interval 1.08-1.92]). Patients were 67.7% females and had a mean age of 22.4 years. The mean opening pressure was 37.9 cmH2O. Anemia was most commonly caused by iron deficiency (51.6%) and aplastic anemia (19.4%). Most patients (59.7%) showed improvement or resolution with anemia treatment only without intracranial pressure-lowering therapy. Evidence was limited because of high risk of reporting bias from the large number of case reports and case-control studies. CONCLUSIONS: Anemia is significantly more common in IIH compared with control patients, and case reports suggest a direct relationship. Complete blood counts should be considered in all patients with papilledema, particularly in atypical presentations (male, nonobese, nonperipapillary retinal hemorrhages, prominent risk factor for anemia) or in treatment-refractory IIH.

Monocular Visual Field Defect on Humphrey 24-2 SITA-Fast Testing Later Identified as a Highly Incongruous Homonymous Defect on Humphrey 30-2 SITA-Fast Testing.

Monocular visual field defects generally localize at or anterior to the optic chiasm, while homonymous hemianopias localize to the retrochiasmal visual pathway. Highly incongruous visual field defects may be difficult to identify on 24-2 Humphrey visual field testing, and this case demonstrates the value of optical coherence tomography (OCT) ganglion cell-inner plexiform layer (GCIPL) in rapidly localizing the lesion. A 54-year-old woman was found on routine examination to have an isolated superonasal quadrant visual field defect respecting the vertical meridian in the left eye only on Humphrey 24-2 SITA-Fast testing. She had a remote history of significant head trauma. Visual acuity, anterior segment, and fundus examination were normal. OCT revealed a bow-tie atrophy of the retinal nerve fiber layer in the right eye (OD), and binocular homonymous hemi-macular atrophy of OCT GCIPL, confirming the localization was the left retrochiasmal visual pathway. A repeat Humphrey 30-2 SITA-Fast visual field demonstrated that the visual field defect was also present in the OD in a highly incongruous manner. Magnetic resonance imaging of the brain with contrast showed mild atrophy of the left optic tract. This case demonstrates that highly incongruous visual field defects may be difficult to identify on Humphrey 24-2 SITA-Fast visual fields, and OCT GCIPL serves as a rapid way to localize the lesion. More detailed visual field testing including 30-2 programs should be considered in these cases.

The Impact of Bariatric Surgery on Diabetic Retinopathy: A Systematic Review and Meta-Analysis.

OBJECTIVE: While bariatric surgery induces remission of type 2 diabetes mellitus and reduces other microvascular complications, its impact on diabetic retinopathy (DR) is unclear. Some trials suggest early worsening of DR postsurgery because of rapid improvements in hyperglycemia. This meta-analysis sought to estimate the impact of bariatric surgery on DR for obese patients compared with medical treatment. DESIGN: Systematic review and meta-analysis. METHODS: The Medline, Embase, and PubMed Central databases were searched to March 2020. Primary studies comparing DR in patients undergoing bariatric surgery with those undergoing medical management were included. Results were meta-analyzed using a random-effects model. Primary outcomes included prevalence of all DR and sight-threatening DR after surgery. Secondary outcomes included worsening of DR within and beyond 12 months. RESULTS: Overall, 14 studies comprised of 110,300 surgical patients and 252,289 control subjects were included. Surgical patients had a statistically significantly lower postoperative prevalence of all DR (relative risk [RR] 0.17 [95% confidence interval {CI} 0.13-0.22]) and sight-threatening DR (RR 0.47 [95% CI 0.27-0.82]). Early worsening of DR and progression to sight-threatening DR had occurred more often in those with more severe DR initially. However, beyond 12 months, bariatric surgery resulted in significantly fewer patients with worsened DR (RR 0.29 [95% CI 0.16-0.54]). The overall risk of bias was low; estimates of relative effects had low to moderate certainty of evidence. CONCLUSION: While bariatric surgery was associated with fewer cases of all and sight-threatening DR, early worsening was more severe in patients with existing sight-threatening DR. These findings argue for frequent monitoring during the first postoperative year.

Topical pain control for corneal abrasions: A systematic review and meta-analysis.

OBJECTIVES: Corneal abrasions are common ophthalmic presentations to emergency departments. Among emergency physicians and ophthalmologists, there are highly variable practice patterns with regard to management of resultant pain and discomfort. The goal of this study was to review and analyze the efficacy and safety of topical pain therapies for corneal abrasions, including topical anesthetics, nonsteroidal anti-inflammatory drugs (NSAIDs), cycloplegics, steroids, pressure patching, and the use of a bandage contact lens (BCL). METHODS: The review followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The protocol was established a priori and published on PROSPERO (CRD42020201288). MEDLINE, EMBASE, CENTRAL, and Web of Science were searched until December 31, 2020. Primary studies comparing topical pain therapies to another therapy or control were included. Primary outcomes included percentage of corneal abrasions healed at 24, 48, and 72 hours, as well as pain control at 24 and 48 hours. Secondary outcomes included use of oral analgesia and incidence of complications. Risk of bias was assessed using validated tools. Quality of evidence was assessed using the GRADE methodology. RESULTS: Overall, 33 studies (31 randomized controlled trials [RCTs], two cohort studies) comprising 4,167 patients with corneal abrasions were analyzed. Only the data for topical NSAIDs were of adequate evidence from which to draw conclusions; topical NSAIDs demonstrated significantly reduced pain scores at 24 hours (standardized mean differences [SMD] -0.69, 95% CI = -0.98 to -0.41) and 48 hours (SMD = -0.56, 95% CI = -1.02 to -0.10) as well as 53% (95% CI = 34% to 67%) lower oral analgesia use compared to control. Based on available data, topical anesthetics, cycloplegics, patching, and the use of a BCL did not result in any significant difference in pain scores or use of oral analgesia, while no studies examined topical steroids. No interventions resulted in healing delays or significantly higher rates of complications compared to controls. CONCLUSIONS: There was strong evidence to support that topical NSAIDs reduce pain associated with corneal abrasions in the first 48 hours and the need for oral analgesia. The existing evidence was insufficient to support or refute the use of topical anesthetics, cycloplegics, steroids, or BCL for pain control in corneal abrasions. Pressure patching was ineffective at pain reduction and may increase the risk of complications. Delays in healing or other complications were not significantly different between any intervention or control for simple, uncomplicated corneal abrasions; however, larger RCTs are required to identify any differences in rare complications.

Use of neuromuscular blocking drugs in strabismus surgery: systematic review and ophthalmology survey study.

OBJECTIVE: Nondepolarizing neuromuscular blocking drugs have been advocated for accurate forced duction testing (FDT) during strabismus surgery. The purpose of this study was to evaluate the literature on use of muscle relaxants (MRs) in strabismus surgery and to evaluate the current practice of pediatric ophthalmologists. DESIGN: Systematic review and survey study. PARTICIPANTS: Seventy-seven pediatric ophthalmologists. METHODS: MEDLINE, EMBASE, CENTRAL, Web of Science, and OpenGrey were searched to August 2019. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Primary studies on depolarizing or nondepolarizing MRs in patients undergoing strabismus surgery were included. Primary outcomes included indications and prevalence of use. A 23-question survey was emailed to pediatric ophthalmologists worldwide to collect practice pattern information involving MRs in strabismus surgery. RESULTS: Three studies were included in the systematic review. MRs were used in 34%-45% of patients undergoing strabismus surgery in one 1999 study for FDT. No evidence exists to support the use of MRs for facilitating FDT. Seven of 77 (9.1%) pediatric ophthalmologists requested MRs for FDT. Those who use MRs were more likely to be practicing outside the United States (p < 0.05) and in academic hospitals or private centres rather than in community settings. Drawbacks appeared to outweigh benefits, with the biggest drawback identified as increased turnover time between surgical cases (44%). CONCLUSIONS: Inadequate evidence exists in the literature to support the use of nondepolarizing MRs to maintain paralysis of extraocular muscles during strabismus surgery, and this is an uncommon practice among pediatric ophthalmologists.

Neuro-ophthalmic Complications of Immune Checkpoint Inhibitors: A Systematic Review.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) are novel cancer therapies that may be associated with immune-related adverse events (IRAEs) and come to the attention of neuro-ophthalmologists. This systematic review aims to synthesize the reported ICI-associated IRAEs relevant to neuro-ophthalmologists to help in the diagnosis and management of these conditions. METHODS: A systematic review of the literature indexed by MEDLINE, Embase, CENTRAL, and Web of Science databases was searched from inception to May 2020. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Primary studies on ICIs and neuro-ophthalmic complications were included. Outcomes included number of cases and incidence of neuro-ophthalmic IRAEs. RESULTS: Neuro-ophthalmic complications of ICIs occurred in 0.46% of patients undergoing ICI and may affect the afferent and efferent visual systems. Afferent complications include optic neuritis (12.8%), neuroretinitis (0.9%), and giant cell arteritis (3.7%). Efferent complications include myasthenia gravis (MG) (45.0%), thyroid-like eye disease (11.9%), orbital myositis (13.8%), general myositis with ptosis (7.3%), internuclear ophthalmoplegia (0.9%), opsoclonus-myoclonus-ataxia syndrome (0.9%), and oculomotor nerve palsy (0.9%). Pembrolizumab was the most common causative agent for neuro-ophthalmic complications (32.1%). Mortality was highest for MG (19.8%). Most patients (79.8%) experienced improvement or complete resolution of neuro-ophthalmic symptoms due to cessation of ICI and immunosuppression with systemic corticosteroids. CONCLUSION: While incidence of neuro-ophthalmic IRAEs is low, clinicians involved in the care of cancer patients must be aware of their presentation to facilitate prompt recognition and management. Collaboration between oncology and neuro-ophthalmology teams is required to effectively manage patients and reduce morbidity and mortality.

Bilateral optic disc edema with preserved visual function not related to papilledema.

Bilateral optic disc edema (ODE) with preserved visual function is typically a result of papilledema, but the causes of this finding in the absence of raised intracranial pressure have not been systematically evaluated. The goal of this study was to determine the causes of bilateral ODE with preserved visual function not related to intracranial hypertension to help in developing a differential diagnosis for this finding. We retrospectively reviewed 221 consecutive patients presenting to a tertiary neuro-ophthalmology practice over a period of 2 years. Four patients met the inclusion criteria with a mean age of 53 years (range 43 to 63), 2 patients were men and 2 were women. The final diagnoses were bilateral optic perineuritis secondary to p-ANCA vasculitis, bilateral incipient non-arteritic anterior ischemic optic neuropathy (NAION), hypertensive emergency, and intermediate uveitis. The patient with NAION developed an inferior altitudinal defect 4 months after presentation, but all other patients maintained normal visual function. The ODE resolved in all cases at a mean follow-up of 4.5 months (range 3 to 6 months). Optic disc edema with preserved visual function may not be related to papilledema, and this series indicates that optic perineuritis, incipient NAION, hypertensive emergency, and intermediate uveitis be considered in the differential diagnosis of these cases.