Immunosuppressive Medications and COVID-19 Outcomes in Patients with Noninfectious Uveitis in the Era of COVID-19 Vaccinations.

Purpose: To determine the risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in the era of COVID-19 vaccination among patients with noninfectious uveitis (NIU) taking immunosuppressive therapies. Design: Retrospective cohort study from July 1, 2021, to June 30, 2022, using data from the Optum Labs Data Warehouse (OLDW) de-identified claims database. Participants: Patients with a diagnosis of NIU from January 1, 2017, and who had ≥ 1 year of continuous enrollment in the OLDW. Methods: Incidence rates (IRs) were calculated for each COVID-19 outcome. Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of systemic corticosteroid (SC) exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models. Main Outcome Measures: Hazard ratios and IRs for COVID-19 infection, hospitalization, and death. Results: This study included 62 209 patients with NIU. A total of 12 895 (20.7%) were exposed to SCs during the risk period. Incidence rates were increased when exposed to SCs versus unexposed for all COVID-19 outcomes. Incidence rates were also increased for all COVID-19 outcomes when exposed to SCs without COVID-19 vaccination versus exposed to SCs with ≥ 1 vaccination. In adjusted models, SCs were associated with increased risk of COVID-19 infection (HR, 3.57; 95% confidence interval [CI], 3.24-3.93; P < 0.0001), hospitalization (HR, 2.75; 95% CI, 2.07-3.65; P < 0.0001), and death (HR, 2.49; 95% CI 1.29-4.82; P = 0.007). Incremental increases in SC dose were associated with a greater risk for all outcomes. Disease-modifying anti-rheumatic drugs were associated with a decreased risk of infection (HR, 0.84; 95% CI, 0.74-0.96; P = 0.01), and tumor necrosis factor-α inhibitors were associated with an increased risk of infection (HR, 1.18; 95% CI, 1.01-1.39; P = 0.04). Conclusions: Systemic corticosteroid exposure continues to be associated with greater risk of COVID-19 infection, hospitalization, and death among patients with NIU in an era of widespread COVID-19 vaccination. Unvaccinated individuals who are exposed to immunosuppressive treatments have a greater risk of severe outcomes. Coronavirus disease 2019 vaccination should be strongly encouraged in these patients. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma.

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperately needed. In this study, we show that elevated expression of 28S rRNA (cytosine-C(5))-methyltransferase NSUN5, which methylates cytosine 3782 of 28S rRNA in GBM cells, is strongly associated with the poor survival of GBM patients. Moreover, we demonstrate that overexpression of NSUN5 increases protein synthesis in GBM cells. NSUN5 knockdown decreased protein synthesis, cell proliferation, sphere formation, migration, and resistance to temozolomide in GBM cell lines. NSUN5 knockdown also decreased the number and size of GBM neurospheres in vitro. As a corollary, mice harboring U251 tumors wherein NSUN5 was knocked down survived longer than mice harboring control tumors. Taken together, our results suggest that NSUN5 plays a protumorigenic role in GBM by enabling the enhanced protein synthesis requisite for tumor progression. Accordingly, NSUN5 may be a hitherto unappreciated target for the treatment of GBM.

Evaluation of cross-platform compatibility of a DNA methylation-based glucocorticoid response biomarker.

BACKGROUND: Identifying blood-based DNA methylation patterns is a minimally invasive way to detect biomarkers in predicting age, characteristics of certain diseases and conditions, as well as responses to immunotherapies. As microarray platforms continue to evolve and increase the scope of CpGs measured, new discoveries based on the most recent platform version and how they compare to available data from the previous versions of the platform are unknown. The neutrophil dexamethasone methylation index (NDMI 850) is a blood-based DNA methylation biomarker built on the Illumina MethylationEPIC (850K) array that measures epigenetic responses to dexamethasone (DEX), a synthetic glucocorticoid often administered for inflammation. Here, we compare the NDMI 850 to one we built using data from the Illumina Methylation 450K (NDMI 450). RESULTS: The NDMI 450 consisted of 22 loci, 15 of which were present on the NDMI 850. In adult whole blood samples, the linear composite scores from NDMI 450 and NDMI 850 were highly correlated and had equivalent predictive accuracy for detecting DEX exposure among adult glioma patients and non-glioma adult controls. However, the NDMI 450 scores of newborn cord blood were significantly lower than NDMI 850 in samples measured with both assays. CONCLUSIONS: We developed an algorithm that reproduces the DNA methylation glucocorticoid response score using 450K data, increasing the accessibility for researchers to assess this biomarker in archived or publicly available datasets that use the 450K version of the Illumina BeadChip array. However, the NDMI850 and NDMI450 do not give similar results in cord blood, and due to data availability limitations, results from sample types of newborn cord blood should be interpreted with care.

DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival.

Assessing individual responses to glucocorticoid drug therapies that compromise immune status and affect survival outcomes in neuro-oncology is a great challenge. Here we introduce a blood-based neutrophil dexamethasone methylation index (NDMI) that provides a measure of the epigenetic response of subjects to dexamethasone. This marker outperforms conventional approaches based on leukocyte composition as a marker of glucocorticoid response. The NDMI is associated with low CD4 T cells and the accumulation of monocytic myeloid-derived suppressor cells and also serves as prognostic factor in glioma survival. In a non-glioma population, the NDMI increases with a history of prednisone use. Therefore, it may also be informative in other conditions where glucocorticoids are employed. We conclude that DNA methylation remodeling within the peripheral immune compartment is a rich source of clinically relevant markers of glucocorticoid response.

The Implications of COVID-19 to Ophthalmology.

The coronavirus disease 2019 (COVID-19) pandemic has brought unprecedented challenges to ophthalmology. At least 16 ophthalmologists worldwide have succumbed to COVID-19. It reflects the susceptibility of ophthalmologists to COVID-19 infection as they are in close proximity to patients. This chapter provides an overview of the ocular manifestations of COVID-19, risks of COVID-19 to ophthalmologists and patients, clinical service adjustments due to COVID-19, and infection control measures to minimize the transmission of COVID-19 in ophthalmic practice.

Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong.

PURPOSE: Coronavirus disease (COVID-19) has rapidly emerged as a global health threat. The purpose of this article is to share our local experience of stepping up infection control measures in ophthalmology to minimise COVID-19 infection of both healthcare workers and patients. METHODS: Infection control measures implemented in our ophthalmology clinic are discussed. The measures are based on detailed risk assessment by both local ophthalmologists and infection control experts. RESULTS: A three-level hierarchy of control measures was adopted. First, for administrative control, in order to lower patient attendance, text messages with an enquiry phone number were sent to patients to reschedule appointments or arrange drug refill. In order to minimise cross-infection of COVID-19, a triage system was set up to identify patients with fever, respiratory symptoms, acute conjunctivitis or recent travel to outbreak areas and to encourage these individuals to postpone their appointments for at least 14 days. Micro-aerosol generating procedures, such as non-contact tonometry and operations under general anaesthesia were avoided. Nasal endoscopy was avoided as it may provoke sneezing and cause generation of droplets. All elective clinical services were suspended. Infection control training was provided to all clinical staff. Second, for environmental control, to reduce droplet transmission of COVID-19, installation of protective shields on slit lamps, frequent disinfection of equipment, and provision of eye protection to staff were implemented. All staff were advised to measure their own body temperatures before work and promptly report any symptoms of upper respiratory tract infection, vomiting or diarrhoea. Third, universal masking, hand hygiene, and appropriate use of personal protective equipment (PPE) were promoted. CONCLUSION: We hope our initial experience in stepping up infection control measures for COVID-19 infection in ophthalmology can help ophthalmologists globally to prepare for the potential community outbreak or pandemic. In order to minimise transmission of COVID-19, ophthalmologists should work closely with local infection control teams to implement infection control measures that are appropriate for their own clinical settings.

Cutaneous ulcer as leading symptom of systemic cytomegalovirus infection.

Cytomegalovirus (CMV) infection rarely manifests with skin ulcerations. We describe a case report of a 64-year-old woman with chronic immunosuppression for treatment of mixed connective tissue disease, presenting with new onset leg ulcerations after a recent change in immunosuppressive regimen. She subsequently developed fulminant hepatitis, encephalopathy, and pancytopenia and was found to have severe systemic CMV viremia. Skin ulcer biopsy was positive by immunohistochemical staining for CMV infected endothelial cells. Both systemic disease and skin ulcer rapidly improved after stopping immunosuppression and administering intravenous ganciclovir. New onset skin ulcers in an immunosuppressed individual, especially with recent changes in immunosuppressive regimen, should raise the suspicion of reactivation of CMV.

Presumed bilateral choroidal metastases from mucoepidermoid carcinoma of the submandibular gland.

PURPOSE: To report a case of presumed bilateral choroidal metastases from mucoepidermoid carcinoma of submandibular gland. METHODS: Case report. A 52-year-old lady with history of left submandibular gland mucoepidermoid carcinoma developed bilateral choroidal metastases unresponsive to chemotherapy. She presented with a 3-week history of left eye pain. Fundoscopy revealed bilateral yellowish choroidal lesions associated with inferior exudative retinal detachment. B-scan ultrasonography showed high internal reflectivity of both lesions. Fluorescein angiography revealed pinpoint foci of hyperfluorescence over the choroidal lesion with late leakage. The patient declined positron emission tomography scan, radiotherapy, and surgical intervention. She eventually succumbed 5 months after the initial presentation. RESULT: Our case is the first case report on clinically presumed bilateral choroidal metastases from mucoepidermoid carcinoma of the submandibular gland. CONCLUSION: There are few reported cases of ocular metastasis from salivary gland tumors, mostly adenoid cystic carcinoma. To the best of our knowledge, this is the first reported case of bilateral choroidal metastases from mucoepidermoid carcinoma of the submandibular gland.

Pseudomonas aeruginosa choroidal abscess in a patient with bronchiectasis.

PURPOSE: To report a case of Pseudomonas aeruginosa endophthalmitis with choroidal abscess formation in a patient with bronchiectasis. METHODS: Case report. RESULTS: A 75-year-old gentleman with bronchiectasis and P. aeruginosa pneumonia developed painless loss of right eye vision. The patient had previously undergone bronchoscopy to exclude pulmonary neoplasm. Slit-lamp examination revealed intense anterior chamber inflammation with hypopyon and B-scan ophthalmic ultrasound showed a choroidal mass consistent with choroidal abscess. Systemic and topical antibiotics did not prevent further progression of the infection. Patient declined pars plana vitrectomy and opted for enucleation. Polymerase-chain-reaction-based restriction fragment-length polymorphism (PCR-RFLP) of the enucleated eye confirmed P. aeruginosa to be the causative organism. CONCLUSION: P. aeruginosa cannot be completely eradicated by systemic antibiotics, and bronchial colonization of P. aeruginosa can remain a potential source for metastatic infection. P. aeruginosa choroidal abscess, previously reported only in patients with cystic fibrosis, can also occur in bronchiectasis. Physicians should therefore have a high index of suspicion of endogenous endophthalmitis and treat aggressively, especially in patients with subretinal invasion and abscess formation.

Encapsulated triamcinolone cyst after subtenon injection.

The authors report the formation of a subtenon cyst following subtenon triamcinolone injection for chronic recurrent uveitis in Behçet's disease. The steroid was inadvertently placed superficially in the anterior subtenon space and was encapsulated eventually to present as a subtenon cyst. The episode of uveitis recurrence, which did not regress, required treatment with a repeat posterior subtenon injection 2 months later. The cyst was removed 4.5 months after the initial subtenon injection, when the patient underwent a trabeculectomy for refractory glaucoma. Histological examination of the cyst revealed a fibrous encapsulated cavity filled with small birefringent crystals, consistent with an encapsulated triamcinolone collection. Fibrous encapsulation of triamcinolone crystals can arise after a superficially placed anterior subtenon injection and this may impede the absorption of the corticosteroid and hamper its effectiveness in treating ocular inflammatory diseases.

The use of peribulbar anaesthesia in paediatric cataract surgery (age 7-15 years) in a mobile eye camp in China.

AIM: To evaluate the feasibility and acceptability of the use of peribulbar anaesthesia (PA) in paediatric cataract surgery in rural areas in China, where there are limitations in expertise and equipment for general anaesthesia (GA). METHODS: We prospectively evaluated the feasibility and acceptability of carrying out paediatric cataract surgery under PA in children aged 7-15 years. Informed consent was obtained from the subjects and their parents. Children were assessed for their suitability for PA. Peribulbar anaesthesia was given as a peribulbar block using a 2% lidocaine, 0.5% bupivacaine-hyaluronidase mixture administered before lens aspiration with intraocular lens implantation. The acceptability of the PA was evaluated by questionnaire. RESULTS: A total of 19 patients were recruited. Their mean age was 12 +/- 2 years (range 7-15 years). None required conversion to GA. All subjects regarded PA as either totally acceptable (63.2%) or acceptable (36.8%). The mean pain scores (from 0 to 100) during the injection and surgery were 28 +/- 26 and 6 +/- 8, respectively. Seventeen patients (89.5%) said they would prefer PA if choices in anaesthesia were offered again. CONCLUSIONS: Peribulbar anaesthesia can be considered as a viable option in selected children undergoing cataract surgery when facilities for safe and optimal general anaesthesia are unavailable.

Pachymetry assessment with Orbscan II in postoperative patients with myopic LASIK.

PURPOSE: To compare central corneal thickness after LASIK for myopia, using ultrasonic pachymetry and Orbscan II measurements, and to evaluate changes in these measurements over time. METHODS: Central corneal thickness measurements obtained by ultrasonic pachymetry and Orbscan II (Bausch and Lomb, Rochester, NY) in patients who underwent myopic LASIK between July 2002 and May 2003 were analyzed. The two measurements were assessed preoperatively and postoperatively at 1 day and 1, 3, 6, and 12 months. RESULTS: In 237 eyes, using the correction factor 0.93, no significant difference was noted in the preoperative central corneal thickness measured by ultrasonic pachymetry (561.89 +/- 28.66 microm) and Orbscan pachymetry (562.28 +/- 28.18 microm) (P =.713). Postoperatively, the difference was statistically significant at day 1 and 1, 3, and 6 months (P < .001), but was not significant at 12 months (P = .130). CONCLUSIONS: Orbscan II measurements of central corneal thickness after myopic LASIK are less than those measured by ultrasonic pachymetry; however, this difference decreases with time and may not be significant after 1 year.

Effect of corneal curvature and corneal thickness on the assessment of intraocular pressure using noncontact tonometry in patients after myopic LASIK surgery.

PURPOSE: To evaluate the effect of corneal curvature and corneal thickness on the assessment of intraocular pressure (IOP) using noncontact tonometry (NCT) in patients after myopic LASIK surgery. METHODS: All patients who had myopic LASIK in a university-based eye clinic between February 2002 and May 2002 were retrospectively analyzed. Preoperative NCT was compared with postoperative NCT, postoperative corneal thickness, and postoperative corneal curvature. RESULTS: The difference between the mean preoperative NCT (15.46 +/- 2.50 mm Hg) and postoperative NCT (6.30 +/- 1.57 mm Hg) was significant (9.16 +/- 1.96 mm Hg, P < 0.010). Preoperative NCT significantly correlated with postoperative NCT (P < 0.001), postoperative corneal thickness (P = 0.006), and postoperative anterior corneal curvature (P < 0.010). CONCLUSIONS: Both corneal thickness and anterior corneal curvature affect IOP assessment in patients with myopic LASIK. Although correction formulas can be used to estimate the actual IOP, alternative methods should be investigated to assess IOP independent of corneal thickness and curvature.

Intravitreal triamcinolone for diabetic macular oedema in Chinese patients: six-month prospective longitudinal pilot study.

AIM: To evaluate the safety and efficacy of intravitreal triamcinolone (IVTA) in Chinese patients with diabetic clinical significant macular oedema (CSMO). METHODS: Eighteen eyes of 17 consecutive patients with CSMO were prospectively recruited and treated with a 4 mg injection of IVTA. Best-corrected visual acuity (BCVA) on the ETDRS chart and central macular thickness (CMT) on optical coherence tomography were measured at baseline weeks 1, 2, 3, and months 1, 2, 3, 4, 5 and 6. Side-effects were monitored. RESULTS: All patients completed 6 months of follow up. The mean baseline BCVA and CMT were 1.20 +/- 0.31 logMAR units and 552 +/- 179 microm, respectively. Improvements in CMT and BCVA were observed as early as at 1 and 2 weeks, respectively (P < 0.05). Mean BCVA peaked at 2 months (0.97 +/- 0.38 logMAR units) while mean CMT was maximally reduced at 3 months (326 +/- 145 microm). Improvements in BCVA and CMT were less afterwards but still statistically significant at 6 months; the final mean BCVA and CMT were 0.99 +/- 0.36 logMAR units and 427 +/- 145 microm, respectively. A total of 5/18 (28%) eyes developed a transient increase in intraocular pressure. Cataract progression was noted in 2/12 (17%) of the phakic eyes. CONCLUSIONS: Intravitreal triamcinolone appeared generally safe and effective in Chinese patients with CSMO. Although the improvements in BCVA and CMT were transient, there were residual benefits at 6 months. Due to the transient nature of IVTA, re-treatment seems necessary but the optimal timing and dosage will require further investigations.