PROPHYLACTIC TREATMENT OF LATTICE DEGENERATION IN FELLOW EYES AFTER REPAIR OF UNCOMPLICATED PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate prophylactic treatment (PTx) of lattice degeneration (LD) on retinal tear (RT) and rhegmatogenous retinal detachment (RRD) risk in fellow eyes of patients after primary RRD repair in the first eye. METHODS: This was a consecutive case series with cohort control involving patients with RRD repair from January 1, 2013, through December 31, 2017. Patients received PTx (PTx cohort) or no PTx (No-PTx cohort) in fellow eye with 5-year follow-up. Primary outcome measure was proportion with new fellow eye RT/RRD. Secondary outcomes included logarithm of minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) and status of myopia, posterior vitreous detachment, and pseudophakia. RESULTS: Four hundred ninety-eight patients were divided into 146 and 352 in PTx and No-PTx cohorts, respectively. PTx cohort developed significantly ( P < 0.05) fewer RT/RRD (17%) than No-PTx cohort (41%). PTx significantly ( P < 0.05) lowered RT/RRD irrespective of posterior vitreous detachment and myopia status. PTx patients undergoing phacoemulsification demonstrated significantly ( P < 0.05) less RT/RRD (22%) than No-PTx cohort (31%). There was no significant ( P = 0.96) final BCVA difference between PTx (median = 0 logMAR) and No-PTx (median = 0 logMAR) cohorts. CONCLUSION: PTx of asymptomatic fellow eye LD reduced RT/RRD risk.

CLINICAL OUTCOMES OF ACUTE ENDOPHTHALMITIS AFTER INTRAVITREAL DELIVERY OF VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS VERSUS STEROIDS.

PURPOSE: To compare patients with acute endophthalmitis after intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors vs. steroids. METHODS: Retrospective single-center, nonrandomized interventional study from 2013 to 2021.Patients underwent vitreous biopsy before initiating treatment and were divided into the following cohorts: (1) anti-VEGF managed medically (T&I-anti-VEGF), (2) anti-VEGF managed by immediate pars plana vitrectomy (PPV-anti-VEGF), and (3) steroid therapy and managed medically or by pars plana vitrectomy (steroid). RESULTS: A total of 141 patients were analyzed. The steroid cohort demonstrated significantly worse presenting (median = 2.80 logarithm of the minimum angle of resolution [logMAR]; P ≤ 0.01) and final (median = 2.30 logMAR) best-corrected visual acuity compared with T&I-anti-VEGF (presenting: median = 2.00 logMAR; final: median = 0.40 logMAR) and pars plana vitrectomy-anti-VEGF cohorts (presenting: median = 2.30 logMAR; final: median = 0.48 logMAR). There was no significant ( P = 0.33) difference in the final best-corrected visual acuity between T&I-anti-VEGF and pars plana vitrectomy-anti-VEGF cohorts. There were no significant ( P ≥ 0.63) differences among cohorts in best-corrected visual acuity before acute endophthalmitis diagnosis (T&I-anti-VEGF: median = 0.40 logMAR; pars plana vitrectomy-anti-VEGF: median = 0.40 logMAR; steroid: median = 0.44 logMAR). Microbial cultures revealed similar profiles for all cohorts. CONCLUSION: Acute endophthalmitis after intravitreal injection steroid therapy had worse outcomes compared with anti-VEGF therapy.

MRI Signal Intensity Varies Along the Course of the Normal Optic Nerve.

BACKGROUND: MRI can help distinguish various causes of optic neuropathy including optic neuritis. Importantly, neuromyelitis optica spectrum disorder (NMOSD) has a propensity to cause enhancement of the prechiasmatic optic nerves. To determine whether the prechiasmatic optic nerve (PC-ON) demonstrates a different intensity from the midorbital optic nerve (MO-ON) on MRI among patients without optic neuropathy. METHODS: Data were retrospectively obtained from 75 patients who underwent brain MRI for an ocular motor nerve palsy between January 2005 and April 2021. Inclusion criteria were patients aged 18 years or older with visual acuities of at least 20/25 and no evidence of optic neuropathy on neuro-ophthalmic examination. A total of 67 right eyes and 68 left eyes were assessed. A neuroradiologist performed quantitative intensity measurements of the MO-ON and PC-ON on precontrast and postcontrast T1 axial images. Normal-appearing temporalis muscle intensity was also measured and used as a reference to calculate an intensity ratio to calibrate across images. RESULTS: The mean PC-ON intensity ratio was significantly higher than the MO-ON intensity ratio on both precontrast (19.6%, P < 0.01) and postcontrast images (14.2%, P < 0.01). Age, gender, and laterality did not independently affect measurements. CONCLUSIONS: The prechiasmatic optic nerve shows brighter intensity ratios on both precontrast and postcontrast T1 images than the midorbital optic nerve among normal optic nerves. Clinicians should recognize this subtle signal discrepancy when assessing patients with presumed optic neuropathy.

Establishing Optic Nerve Diameter Threshold Sensitive and Specific for Optic Atrophy Diagnosis.

PURPOSE: To determine a potential threshold optic nerve diameter (OND) that could reliably differentiate healthy nerves from those affected by optic atrophy (OA) and to determine correlations of OND in OA with retinal nerve fiber layer (RNFL) thickness, visual acuity (VA), and visual field mean deviation (VFMD). METHODS: This was a retrospective case control study. Magnetic resonance (MR) images were reviewed from individuals with OA aged 18 years or older with vision loss for more than 6 months and an OA diagnosis established by a neuro-ophthalmologist. Individuals without OA who underwent MR imaging of the orbit for other purposes were also collected. OND was measured on coronal T2-weighted images in the midorbital section, 1cm posterior to the optic disc. Measurements of mean RNFL thickness, VA and VFMD were also collected. RESULTS: In this study 47 OA subjects (63% women, 78 eyes) and 75 normal subjects (42.7% women, 127 eyes) were assessed. Healthy ONDs (mean 2.73 ± 0.24 mm) were significantly greater than OA nerve diameters (mean 1.94 ± 0.32 mm; P < 0.001). A threshold OND of ≤2.3 mm had a sensitivity of 0.92 and a specificity of 0.93 in predicting OA. Mean RNFL (r = 0.05, p = 0.68), VA (r = 0.17, p = 0.14), and VFMD (r = 0.18, p = 0.16) were not significantly associated with OND. CONCLUSION: ONDs are significantly reduced in patients with OA compared with healthy nerves. A threshold OND of ≤2.3 mm is highly sensitive and specific for a diagnosis of OA. OND was not significantly correlated with RNFL thickness, VA, or VFMD.

Evaluation of Outcomes of Acute Cataract Surgery-Related Endophthalmitis Using a Novel Management Algorithm Based on Presenting Risk Factors.

PURPOSE: Develop treatment algorithm for acute endophthalmitis (AE) following cataract surgery. METHODS: Retrospective single-center, non-randomized interventional study involving patients with AE divided into cohorts according to our novel scoring system, the Acute Cataract surgery-related Endophthalmitis Severity (ACES) score. Total score ≥3 points indicated need for urgent pars plana vitrectomy (PPV; within 24 hours), whereas <3 points indicated urgent PPV was unnecessary. Patients were retrospectively evaluated for visual outcomes based on whether their clinical course followed with or deviated from ACES score recommendations. Main outcome was best-corrected visual acuity (BCVA) at 6-month or longer after treatment. RESULTS: Total of 150 patients were analyzed. Patients whose clinical course followed the ACES score recommendation for immediate surgery had significantly (P < 0.01) better final BCVA (median = 0.18 logMAR, 20/30 Snellen) compared to those that deviated (median = 0.70 logMAR, 20/100 Snellen). For those where the ACES score deemed urgent PPV was unnecessary, no significant (P = 0.19) difference was observed between patients that followed with (median = 0.18 logMAR, 20/30 Snellen) and those that deviated from (median = 0.10 logMAR, 20/25 Snellen) recommendation. CONCLUSIONS: The ACES score may potentially provide critical and updated management guidance at presentation for when to recommend urgent PPV for patients suffering from post-cataract surgery AE.

Clinical Factors and Outcomes of Acute-Onset Endophthalmitis Following Small-Gauge Pars Plana Vitrectomy Surgery.

BACKGROUND AND OBJECTIVES: Describe risk factors, findings, and outcomes of acute endophthalmitis (AE) following small-gauge pars plana vitrectomy (PPV). PATIENTS AND METHODS: This was a retrospective single-center, nonrandomized study of post-PPV AE patients from 2013 to 2021. All received vitreous biopsy before treatment. Patients were divided into cohorts: 1) PPV within 3 days of diagnosis (Urgent-PPV), and 2) no urgent PPV (Other-treatment [Tx]). Main outcome was best-corrected visual acuity (BCVA) at 6 months. RESULTS: Twenty-one patients were analyzed. Epiretinal membrane was the most common indication for PPV (48%). Incidence was 0.074%. Culture-positive rate was 57%. For final BCVA, there was no significant (P = 0.85) difference between Urgent-PPV (median = 0.40 logMAR) and Other Tx cohorts (median = 0.35 logMAR). Sclerotomy wounds were not sutured in 71% of patients. Approximately 24% and 38% of patients analyzed had either no tamponade or partial tamponade, respectively. CONCLUSION: Tamponade agents and sclerotomy suturing may be important factors when evaluating post-small-gauge PPV-associated AE. Further studies are necessary for clarification. [Ophthalmic Surg Lasers Imaging Retina 2023;54:395-400.].

PAX8/PAX8-AS1 DNA methylation levels are associated with objective sleep duration in persons with unexplained hypersomnolence using a deep phenotyping approach.

STUDY OBJECTIVES: Patients with unexplained hypersomnolence have significant impairment related to daytime sleepiness and excessive sleep duration, the biological bases of which are poorly understood. This investigation sought to examine relationships between objectively measured hypersomnolence phenotypes and epigenetic modification of candidate hypersomnolence genes to advance this line of inquiry. METHODS: Twenty-eight unmedicated clinical patients with unexplained hypersomnolence were evaluated using overnight ad libitum polysomnography, multiple sleep latency testing, infrared pupillometry, and the psychomotor vigilance task. DNA methylation levels on CpG sites annotated to 11 a priori hypersomnolence candidate genes were assessed for statistical association with hypersomnolence measures using independent regression models with adjusted local index of significance (aLIS) P-value threshold of 0.05. RESULTS: Nine CpG sites exhibited significant associations between DNA methylation levels and total sleep time measured using ad libitum polysomnography (aLIS p-value < .05). All nine differentially methylated CpG sites were annotated to the paired box 8 (PAX8) gene and its related antisense gene (PAX8-AS1). Among these nine differentially methylated positions was a cluster of five CpG sites located in the body of the PAX8 gene and promoter of PAX8-AS1. CONCLUSIONS: This study demonstrates that PAX8/PAX8-AS1 DNA methylation levels are associated with total sleep time in persons with unexplained hypersomnolence. Given prior investigations that have implicated single nucleotide polymorphisms in PAX8/PAX8-AS1 with habitual sleep duration, further research that clarifies the role of DNA methylation levels on these genes in the phenotypic expression of total sleep time is warranted.

Multimodal assessment increases objective identification of hypersomnolence in patients referred for multiple sleep latency testing.

STUDY OBJECTIVES: The multiple sleep latency test (MSLT) has limitations when evaluating disorders of hypersomnolence with unknown etiology. Alternative measures of hypersomnolence may objectively identify pathology in patients with complaints of daytime sleepiness that may not be captured by the MSLT alone. This study evaluated the impact of a multimodal hypersomnolence assessment relative to MSLT in patients with unexplained hypersomnolence. METHODS: Seventy-five patients with unexplained hypersomnolence were included in the analyzed sample. Polysomnography was performed without prescribed wake time, and the psychomotor vigilance task and pupillographic sleepiness test were completed between MSLT nap opportunities. Presence or absence of hypersomnolence for each assessment was defined using a priori cutpoints. Proportions of patients identified as hypersomnolent using the multimodal assessment relative to MSLT alone were evaluated, as well as the sensitivity and specificity of ancillary hypersomnolence measures relative to MSLT as a gold standard. RESULTS: The multimodal assessment more than doubled the proportion of patients identified as having objective deficits relative to MSLT ≤ 8 minutes alone. The combination of excessive sleep duration, lapses on the psychomotor vigilance task, and impairments on the pupillographic sleepiness test also had perfect sensitivity in identifying all patients identified as sleepy by the MSLT across 3 different MSLT cutpoints (5, 8, and 10 minutes). CONCLUSIONS: These data demonstrate the insufficiency of the MSLT as a singular tool to identify objective pathology in persons with unexplained hypersomnolence. Further efforts to refine and standardize multimodal assessments will likely improve diagnostic acumen and research into the causes of these disorders.

Optimizing Actigraphic Estimation of Sleep Duration in Suspected Idiopathic Hypersomnia.

STUDY OBJECTIVES: To determine the optimal Actiwatch 2 setting configuration for the estimation of total sleep time (TST) in persons with suspected idiopathic hypersomnia. METHODS: Thirty-three patients with a diagnosis of idiopathic hypersomnia (28 female; mean age = 33.7 ± 10.5) underwent ad libitum polysomnography with concurrent use of the Actiwatch 2. Actiwatch 2 sleep-wake activity threshold (SWAT; Low, Medium, and High) and sleep immobility onset and offset (SIOO; 5, 10, 15, 20, 25, and 30 epoch) duration were modified during data processing. The resultant 18 unique setting combinations were subsequently evaluated using Bland-Altman and epoch comparison analyses to determine optimal settings relative to polysomnography. RESULTS: Low SWAT + 25 Epoch SIOO displayed the least divergence from polysomnography (mean difference 3.4 minutes). Higher SWAT and lower SIOO increased sensitivity and accuracy, but at the expense of reducing specificity and the ability to accurately estimate TST. CONCLUSIONS: These results demonstrate that actigraphic settings should be carefully considered when estimating sleep duration. The Low + 25 Epoch configuration is indicated as most optimal for estimating TST in persons with suspected idiopathic hypersomnia. COMMENTARY: A commentary on this article appears in this issue on page 539.

Utility of the Compensatory Tracking Task for Objective Differentiation of Hypersomnolence in Depression: A High-Density EEG Investigation.

Hypersomnolence is a common and debilitating symptom in mood disorders. However, objective differentiation of excessive daytime sleepiness (EDS) from non-EDS in depression has not yet been achieved. This study compared performance on the Compensatory Tracking Task (CTT) and concurrently-recorded high-density (hd)EEG theta power in 22 patients with major depressive disorder (MDD) and co-occurring EDS against 22 age- and sex-matched patients with MDD but no EDS, as well as 22 age- and sex-matched healthy controls. Though depressed hypersomnolent participants endorsed feeling sleepier than depressed non-hypersomnolent and healthy control participants prior to starting the CTT, no group differences in CTT performance were observed. Average hdEEG theta power was higher during periods of high error on the CTT compared to periods of low error, but did not differ between the groups. Though the CTT still holds promise as an objective neurobehavioral measure, these results do not indicate a capability to differentiate EDS from non-EDS in mood disorders.

Establishing the objective sleep phenotype in hypersomnolence disorder with and without comorbid major depression.

STUDY OBJECTIVES: To clarify whether hypersomnolence disorder is associated with a specific sleep phenotype and altered neurophysiological function in persons with and without hypersomnolence disorder and major depressive disorder (MDD). METHODS: Eighty-three unmedicated persons with and without hypersomnolence disorder and/or MDD underwent ad libitum high-density EEG polysomnography. Clinical and sleep architecture variables were compared between groups. Topographic patterns of slow-wave activity (SWA) relative to healthy controls were compared, with correlations between topographic SWA and daytime sleepiness assessed. Reductions in SWA in hypersomnolence disorder were mapped to specific cortical areas using source localization. RESULTS: Regardless of the presence or absence of comorbid MDD, persons with hypersomnolence disorder had increased sleep duration relative to both controls and persons with MDD without hypersomnolence. Participants with hypersomnolence disorder also demonstrated reduced bilateral centroparietal low-frequency activity during nonrapid eye movement sleep relative to controls, a pattern not observed in persons with MDD but without hypersomnolence. SWA in these regions was negatively correlated with subjective measures of daytime sleepiness. Source localization demonstrated reductions in SWA in the supramarginal gyrus, somatosensory, and transverse temporal cortex in participants with hypersomnolence disorder. CONCLUSIONS: Hypersomnolence disorder is characterized by increased sleep duration with normal sleep continuity, regardless of the presence or absence of comorbid depression. Reduced local SWA may be a specific neurophysiological finding in hypersomnolence disorder. Further research is warranted to elucidate the mechanisms through which these cortical changes are related to clinical complaints of daytime sleepiness.

Ability of the Multisensory Jawbone UP3 to Quantify and Classify Sleep in Patients With Suspected Central Disorders of Hypersomnolence: A Comparison Against Polysomnography and Actigraphy.

STUDY OBJECTIVES: To evaluate the ability of a multisensory fitness tracker, the Jawbone UP3 (JB3), to quantify and classify sleep in patients with suspected central disorders of hypersomnolence. METHODS: This study included 43 patients who completed polysomnography (PSG) and a Multiple Sleep Latency Test (MSLT) with concurrent wrist-worn JB3 and Actiwatch 2 (AW2) recordings for comparison. Mean differences in nocturnal sleep architecture variables were compared using Bland-Altman analysis. Sensitivity, specificity, and accuracy were derived for both devices relative to PSG. Ability of the JB3 to detect sleep onset rapid eye movement periods (SOREMPs) during MSLT naps was also quantified. RESULTS: JB3 demonstrated a significant overestimation of total sleep time (39.6 min, P < .0001) relative to PSG, but performed comparably to AW2. Although the ability of the JB3 to detect epochs of sleep was relatively good (sensitivity = 0.97), its ability to distinguish light, deep, and REM sleep was poor. Similarly, the JB3 did not correctly identify a single SOREMP during any MSLT nap opportunity. CONCLUSIONS: The JB3 did not accurately quantify or classify sleep in patients with suspected central disorders of hypersomnolence, and was particularly poor at identifying REM sleep. Thus, this device cannot be used as a surrogate for PSG or MSLT in the assessment of patients with suspected central disorders of hypersomnolence.

Utility of the Fitbit Flex to evaluate sleep in major depressive disorder: A comparison against polysomnography and wrist-worn actigraphy.

BACKGROUND: Sleep disturbance is a common and important component of affective illness. Fitness activity trackers are emerging as alternative means to estimate sleep in psychiatric patients; however, their ability to quantify sleep in mood disorders has not been empirically evaluated. Thus, this study sought to evaluate the utility of the Fitbit Flex (FBF) to estimate sleep in patients with major depressive disorder (MDD) relative to gold standard polysomnography (PSG) and a widely-used actigraph (Actiwatch-2; AW-2). METHODS: Twenty-one patients with unipolar MDD wore the FBF and AW-2 during in-laboratory PSG. Bland-Altman analysis compared sleep variables among devices. Epoch-by-epoch analysis further evaluated sensitivity, specificity, and accuracy for the FBF and AW-2 relative to PSG. RESULTS: The FBF demonstrated significant limitations in quantifying sleep and wake, relative to PSG. In the normal setting, the FBF significantly overestimated sleep time and efficiency, and displayed poor ability to correctly identify wake epochs (i.e. low specificity). In the sensitive setting, the FBF significantly underestimated sleep time and efficiency relative to PSG. Performance characteristics of the FBF were more similar to the AW-2 in the normal compared to sensitive setting. LIMITATIONS: Participants were young to middle aged and predominantly female, which may limit generalizability of findings. Study design also precluded ability to assess longitudinal performance of FBF. CONCLUSIONS: The FBF is not an adequate substitute for PSG when quantifying sleep in MDD, and the settings of the device sizably impact its performance relative to PSG and other standard actigraphs. The limitations and capabilities of the FBF should be carefully considered prior to clinical and research implementation.