TACROLIMUS FOR IMMUNOSUPPRESSION IN PATIENTS WITH NONINFECTIOUS INTERMEDIATE, POSTERIOR, OR PANUVEITIDES.

PURPOSE: To evaluate the effectiveness of tacrolimus in patients with noninfectious intermediate, posterior, or panuveitis needing a two-immunosuppressive-agent regimen. METHODS: Design: Retrospective cohort study. Setting: Two tertiary-care uveitis practices at academic medical centers. Patient population: Thirty-two patients with noninfectious intermediate, posterior, or panuveitides in whom single-agent immunosuppression was inadequate to effect successful corticosteroid sparing. Intervention: tacrolimus, added as the second immunosuppressive agent. Main outcome measure: successful corticosteroid sparing, defined as inactive uveitis at a dose of prednisone ≤7.5 mg/day. RESULTS: Active uveitis was present in 65.6% of patients at initiation of tacrolimus, and the median time to inactive uveitis was 1.5 months (95% confidence interval 1.2, 4.08). The median time to successful corticosteroid sparing was 3.9 months (95% confidence interval 1.41, 6.67), and by 6 months of follow-up successful corticosteroid sparing was achieved in 75% of patients. Tacrolimus was discontinued for side effects in five patients, three for tremor, and two for hyperglycemia. All side effects were reversible with tacrolimus discontinuation. CONCLUSION: Tacrolimus seems to have efficacy as a second immunosuppressive agent in two-immunosuppressive drug regimens, when a single agent does not permit successful corticosteroid sparing. Side effects were reversible with tacrolimus discontinuation.

Changes in patient visits and diagnoses in a large academic center during the COVID-19 pandemic.

BACKGROUND: To minimize the risk of viral transmission, ophthalmology practices limited face-to-face encounters to only patients with urgent and emergent ophthalmic conditions in the weeks after the start of the COVID-19 epidemic in the United States. The impact of this is unknown. METHODS: We did a retrospective analysis of the change in the frequency of ICD-10 code use and patient volumes in the 6 weeks before and after the changes in clinical practice associated with COVID-19. RESULTS: The total number of encounters decreased four-fold after the implementation of clinic changes associated with COVID-19. The low vision, pediatric ophthalmology, general ophthalmology, and cornea divisions had the largest total decrease of in-person visits. Conversely, the number of telemedicine visits increased sixty-fold. The number of diagnostic codes associated with ocular malignancies, most ocular inflammatory disorders, and retinal conditions requiring intravitreal injections increased. ICD-10 codes associated with ocular screening exams for systemic disorders decreased during the weeks post COVID-19. CONCLUSION: Ophthalmology practices need to be prepared to experience changes in practice patterns, implementation of telemedicine, and decreased patient volumes during a pandemic. Knowing the changes specific to each subspecialty clinic is vital to redistribute available resources correctly.

Retinal Nerve Fibre Layer Thickness Increases with Decreasing Spectralis OCT Signal Strength in Normal Eyes.

We sought to determine effect of signal strength on mean retinal nerve fibre layer (RNFL) using Spectralis optical coherence tomography (S-OCT). Thirty normal subjects (18 female, mean 37.9 years, range 24-61) were imaged with S-OCT using variably dense Bangerter foils to alter Q value (1 unit signal strength = 4 units Q). We found a statistically significant (p < 0.01) linear relationship (R = 0.8643) between Q and RNFL (1 unit decrease Q = 0.181 um mean RNFL increase). Unlike previous observations of Cirrus and Stratus OCT, we found RNFL thickness does not decrease with decreasing signal strength in S-OCT.

Is there treatment for traumatic optic neuropathy?

PURPOSE OF REVIEW: The purpose of this study is to discuss current controversies surrounding the proposed treatments for traumatic optic neuropathy (TON) and review recent evidence from the literature relating to these therapeutic options. RECENT FINDINGS: No recent randomized controlled trials investigating surgical or medical interventions for TON exist. The current literature regarding treatment of TON consists mainly of small, mostly retrospective, observational studies. Treatment of TON with corticosteroids, surgical decompression of the optic canal or combinations of surgery and corticosteroids does not appear to offer improved visual outcomes compared with observation alone. Recent evidence suggests that there may be diminished functional reserve of the optic nerve following trauma. Novel neuroprotective therapies, such as erythropoietin, are currently under investigation in the treatment of TON. SUMMARY: TON may lead to profound visual disability. Because of the absence of Class I evidence relating to treatment of TON, a lack of consensus exists among clinicians regarding the appropriate treatment for TON. Our review of the recent literature finds that there is still no reliable evidence that treatment of TON with corticosteroids, surgical optic canal decompression or both confers any benefit over observation alone, and yet these interventions incur an additional risk that may not warrant their routine use.

Using the Electronic Medical Record to Increase Laboratory Test Monitoring in Ocular Inflammation Patients: A Quality Improvement Study.

BACKGROUND AND OBJECTIVES: Treatment of chronic, noninfectious ocular inflammation includes corticosteroids, disease-modifying antirheumatic medications, and biologics. To mitigate adverse effects associated with the use of these medications, routine laboratory test monitoring is recommended throughout treatment. We evaluated the effectiveness of an alert added to the electronic medical record (EMR) to aid in laboratory test monitoring for patients prescribed these high-risk medications. METHODS: A prospective, interventional study assessed the effect of the alert within the EMR on laboratory test ordering at the Division of Ocular Immunology at the Wilmer Eye Institute. The primary outcome measure was the change in number of ordered laboratory tests at 3, 6, and 12 months after the alert activation compared with pre-intervention levels and overall through the study period. The laboratory tests that were monitored included complete blood count, comprehensive metabolic panel, dual-energy x-ray absorptiometry (DXA) scanning, fasting lipid panel, and interferon gamma release assays. RESULTS: The laboratory test orders for 153 patients on high risk medications were analyzed. Only the frequency of ordering the DXA and interferon gamma release assays increased significantly, compared with baseline, throughout the study. Conversely, there was a significant decrease in the frequency of ordering of fasting lipid profiles and hemoglobin A 1c at each time point and for complete blood count and comprehensive metabolic panel at the 6-month time point. CONCLUSION: An EMR alert results in increased laboratory test ordering initially for tests drawn on a yearly basis, but the effect on more frequently ordered tests wanes with time if the alert can be silenced by the provider. Nonetheless, it provides a novel mechanism to increase laboratory ordering in patients on high-risk medications that can be adapted for use in other EMR software. Future studies are needed to assess whether physician laboratory test ordering behavior is altered throughout the study period with the use of a non-silencable alert.

Effectiveness of the Dexamethasone Implant in Lieu of Oral Corticosteroids in Intermediate and Posterior Uveitis Requiring Immunosuppression.

PURPOSE: To evaluate dexamethasone intravitreal implant effectiveness in lieu of high-dose oral prednisone for short-term treatment of noninfectious intermediate and posterior uveitis in patients requiring immunosuppression. METHODS: This is a proof-of-concept, open-label, non-comparative clinical trial with 12-month follow-up. The primary outcome was uveitis control without additional prednisone at 6 and 12 months. Secondary outcomes were need for multiple implants or additional prednisone, and safety data. RESULTS: 20 patients (28 eyes) were enrolled- 16 eyes had control by 6 months; 20 by 12 months. No patients required high-dose prednisone. 6 patients enrolled on prednisone: 2 stopped; 4 tapered to 7.5 mg daily or less by 12 months. 16 eyes required multiple implants; five required cataract surgery; 12 required drops to control IOP; 2 underwent glaucoma surgery. CONCLUSIONS: The dexamethasone implant was effective in lieu of high-dose prednisone although the majority required multiple implants. All patients decreased or discontinued prednisone during follow-up.

Ocular Complications of Checkpoint Inhibitors and Immunotherapeutic Agents: A Case Series.

Background: Ophthalmologists have a role in assessing immune-related adverse events (IRAE) in oncology patients on immunotherapy. We assessed the utility of a hospital-wide toxicity team in referring patients with new ocular symptoms for examination. We also identified new immunotherapy agents causing ocular side-effects.Design: A cohort study of eight consecutive patients on immunotherapy, who developed ocular IRAE from November 1, 2017 to June 30, 2019. All were seen at the Ocular Immunology Division of the Wilmer Eye Institute and referred by the Johns Hopkins Toxicity Team.Results: All eight patients on had IRAEs; were treated with corticosteroid drops or observation with clinical resolution. Two new agents, epocadostat and daratumumab, were associated with the development of uveitis.Conclusion: Ophthalmologists play an important role in a hospital-wide toxicity team and need to include IRAEs in their differential diagnosis. Given new drug development, ophthalmologists may be the first to identify IRAEs.

Escalation to Weekly Adalimumab for the Treatment of Ocular Inflammation.

Purpose: To report the outcomes of the escalation of adalimumab (ADA) dose for refractory ocular inflammatory diseases.Methods: A retrospective case series of 15 patients (29 eyes) diagnosed with ocular inflammatory disease, including uveitis and scleritis, which was not adequately controlled with standard, every other week ADA dosing, leading to an escalation to weekly dosing.Results: Ten of fifteen patients escalated to weekly ADA achieved control of their inflammation; neither of the two patients increased for control of cystoid macular edema (CME) had resolution and required regional corticosteroids. One patient discontinued weekly ADA due to serious infection. The median length of follow up was 12 months.Conclusion: Our series suggests that the escalation of ADA can be a useful strategy for treating recalcitrant ocular inflammation, but may not be adequate to treat refractory CME.

Broadly sampled multigene trees of eukaryotes.

BACKGROUND: Our understanding of the eukaryotic tree of life and the tremendous diversity of microbial eukaryotes is in flux as additional genes and diverse taxa are sampled for molecular analyses. Despite instability in many analyses, there is an increasing trend to classify eukaryotic diversity into six major supergroups: the 'Amoebozoa', 'Chromalveolata', 'Excavata', 'Opisthokonta', 'Plantae', and 'Rhizaria'. Previous molecular analyses have often suffered from either a broad taxon sampling using only single-gene data or have used multigene data with a limited sample of taxa. This study has two major aims: (1) to place taxa represented by 72 sequences, 61 of which have not been characterized previously, onto a well-sampled multigene genealogy, and (2) to evaluate the support for the six putative supergroups using two taxon-rich data sets and a variety of phylogenetic approaches. RESULTS: The inferred trees reveal strong support for many clades that also have defining ultrastructural or molecular characters. In contrast, we find limited to no support for most of the putative supergroups as only the 'Opisthokonta' receive strong support in our analyses. The supergroup 'Amoebozoa' has only moderate support, whereas the 'Chromalveolata', 'Excavata', 'Plantae', and 'Rhizaria' receive very limited or no support. CONCLUSION: Our analytical approach substantiates the power of increased taxon sampling in placing diverse eukaryotic lineages within well-supported clades. At the same time, this study indicates that the six supergroup hypothesis of higher-level eukaryotic classification is likely premature. The use of a taxon-rich data set with 105 lineages, which still includes only a small fraction of the diversity of microbial eukaryotes, fails to resolve deeper phylogenetic relationships and reveals no support for four of the six proposed supergroups. Our analyses provide a point of departure for future taxon- and gene-rich analyses of the eukaryotic tree of life, which will be critical for resolving their phylogenetic interrelationships.

A checklist of the mosquitoes of Indiana with notes on the cryptic species complexes Anopheles quadrimaculatus s.l. and Anopheles punctipennis.

The checklist of the mosquito species reported to occur in the state of Indiana is updated to include a number of new records and new classifications. Specimens of the cryptic species complex Anopheles quadrimaculatus s.1. are identified as An. quadrimaculatus s.s., and specimens of An. punctipennis are identified as the Eastern form of the species.

Peripheral Cryoablation for Treatment of Active Pars Planitis: Long-Term Outcomes of a Retrospective Study.

PURPOSE: To compare the long-term outcomes of peripheral retinal cryoablation to conventional treatment for active pars planitis. DESIGN: Retrospective, interventional, comparative case series. METHODS: Review at a single institution was conducted to compare the effect of cryotherapy to eyes with pars planitis to those receiving conventional therapy (topical, regionally injected, or oral corticosteroid therapy). Best-corrected visual acuity (VA), complications, resolution of cystoid macular edema (CME), and anterior chamber and vitreous inflammation were assessed. RESULTS: One hundred thirty-six eyes were treated conventionally, 50 eyes were treated with cryotherapy. Median follow-up was 60.8 months (range 8.1-223.1 months) in the cryotherapy group and 45.0 months (range 3.1-339.0 months) in the controls. There were no significant differences in baseline VA, anterior chamber and vitreous inflammation, presence of CME, and prior use of regional corticosteroid injections. VA improved over time in the cryotherapy group (slope of -0.0018 logMAR units per month; P = .023) but declined in the controls (slope of +0.0011 logMAR units per month; P = .023). Kaplan-Meier survival estimates demonstrated faster times to resolution of anterior chamber cell, vitreous cell, and CME in the cryotherapy-treated eyes. Hazard ratios of remission (adjusted for confounding factors) for vitreous cell and CME for those treated with cryotherapy compared to controls were 4.73 (95% confidence interval 1.63, 13.63; P = .004) and 6.85 (95% confidence interval 1.06, 44.78; P = .044), respectively. No ocular complications were identified in the cryotherapy group. CONCLUSIONS: These data suggest that peripheral retinal cryoablation therapy is an effective treatment for active pars planitis and may be better than conventional regional corticosteroid injections and oral corticosteroid therapy for induction of remission.