March 2020

The delivery of ophthalmic drugs is challenging despite easy accessibility via the ocular surface. Topical instillation of eye drops is a relatively easy and most commonly used as a conduit for drug delivery for treating a myriad of ocular morbidities, particularly involving the anterior segment, and has an additional benefit of avoiding the first-pass metabolism while passing through the systemic circulation. The primary challenges of drug administration through traditional methods include-inadequate patient education for proper drug instillation technique, compliance, adherence, and persistence. Various dynamic (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) and static (namely, different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers) ocular barriers limit drug delivery to the target ocular tissues. The maintenance of the therapeutic drug levels on the ocular surface for a prolonged duration is an added challenge, thus preventing persistent delivery for longer durations. These factors result in inadequate management, leading to poor prognosis in vision loss in as many as 27% of the patients diagnosed with glaucoma. We have reviewed the research and advancements in the development of novel and well-tolerated drug delivery systems with the common goal of overcoming the factors limiting adequate drug delivery to the target tissues in glaucomatous patients with traditional techniques. In the recent past, multiple research groups have successfully designed noninvasive, sustained drug delivery systems, promoting the efficacy as well as the feasibility of delivering topical drugs to the anterior segment.

PURPOSE OF REVIEW: Current recommendations for glaucoma screening are decidedly neutral. No studies have yet documented improved long-term outcomes for individuals who undergo glaucoma screening versus those who do not. Given the long duration that would be required to detect a benefit, future studies that may answer this question definitively are unlikely. Nevertheless, advances in artificial intelligence and telemedicine will lead to more effective screening at lower cost. With these new technologies, additional research is needed to determine the costs and benefits of screening for glaucoma. RECENT FINDINGS: Using optic disc photographs and/or optical coherence tomography, deep learning systems appear capable of diagnosing glaucoma more accurately than human graders. Eliminating the need for expert graders along with better technologies for remote imaging of the ocular fundus will allow for less expensive screening, which could enable screening of individuals with otherwise limited healthcare access. In India and China, where most glaucoma remains undiagnosed, glaucoma screening was recently found to be cost-effective. SUMMARY: Recent advances in artificial intelligence and telemedicine have the potential to increase the accuracy, reduce the costs, and extend the reach of screening. Further research into implementing these technologies in glaucoma screening is required.

The prevalence of dry eye disease is high worldwide and poses a great burden on patients' daily lives. Accurate diagnosis of the disease is important, and it requires application of various methods. Hyperosmolarity is believed to be the disease marker and thus measuring it provides useful information. In this study we investigated utility of tear osmolarity measured with TearLab osmometer, along with other diagnostic tests (Ocular Surface Disease Index questionnaire, Tear film break-up time, Ocular Protection Index, Ocular Surface Staining, Schirmer I test, Meibomian gland functionality in 757 patients (1514 eyes) with dry eye disease and 29 healthy controls (58 eyes). Statistical differences between the patient group and the control group were observed for all the tests apart from tear osmolarity, regardless of cut-off value (>308 mOsm/L, >316 mOsm/L, and inter-eye difference >8 mOsm/L). Moreover, in the receiver operating characteristics curve analyses tear osmolarity measurement could not discriminate dry eye disease pathological scores. Therefore, our study suggests that tear osmolarity measured with TearLab osmometer cannot be used as a key indicator of DED.

SIGNIFICANCE: Electronic display devices used before bed may negatively affect sleep quality through the effects of short-wavelength (blue) light on melatonin production and the circadian cycle. We quantified the efficacy of night-mode functions and blue-light-reducing lenses in ameliorating this problem. PURPOSE: The purpose of this study was to compare the radiation produced by smartphones that reaches the eye when using night-mode functions or blue-light-reducing spectacle lenses. METHODS: Radiant flux of 64 smartphones was measured with an integrating sphere. The retinal illuminance was calculated from the radiant flux of the smartphones. For the night-mode functions, the spectra produced by the smartphones were measured. The transmittance of four blue-light-reducing spectacle lenses, which filter light with either antireflective coatings or tints, was measured using a spectrometer. To determine the impact of blue-light-reducing spectacles, the radiant flux of the smartphone was weighted by the transmission spectrum of these glasses. Visual and nonvisual (circadian) parameters were calculated to compute the melatonin suppression values (MSVs) through a logistic fitting of previously published data. The MSV was used as the figure of merit to evaluate the performance of blue-light spectacles and smartphone night-mode functions. RESULTS: Night-mode functions in smartphones reduced MSVs by up to 93%. The warmest mode produced the least suppression. Blue-light-reducing spectacles reduced melatonin suppression by 33%, the coated lenses being more efficient than tinted lenses. CONCLUSIONS: All smartphones in this study emit radiant power in the short-wavelength region of the visible spectrum. Such smartphones may impair the regulation of circadian cycles at nighttime. The activation of night-mode functions was more efficient than the commercially available blue-light-reducing spectacle lenses in reducing the amount of short-wavelength light (up to 2.25 times). These results can be extrapolated to most electronic devices because they share the same type of white radiant sources with smartphones.

Purpose: To present a novel case of sarcoid choroidal granulomas due to nivolumab therapy for metastatic cutaneous melanoma. Observations: A 55 year-old male with a history of stage III metastatic cutaneous melanoma treated by nivolumab presented with bilateral choroidal lesions. The ophthalmologic examination revealed bilateral creamy, yellow choroidal lesions with no ocular inflammation. The systemic workup revealed pulmonary sarcoidosis confirmed by biopsy. Conclusion: Nivolumab is an immune checkpoint inhibitor therapy used in the treatment of metastatic melanoma. With the increasing use of immune checkpoint inhibitors in patients with advanced melanoma, clinicians should be aware of this potential associated immune-related adverse event.

Purpose: bacteriemia (SAB) as critical condition for the life and occasionally involves the eyes. The aim of this report is to describe the ocular involvement with multimodal imaging. Observations: A patient admitted for evaluation of acute onset of confusion, disorientation, and generalized malaise and found to have methicillin-resistant staphylococcus aureus (MRSA)-associated endocarditis and multifocal brain abscesses was evaluated by the ophthalmology service. The patient's visual acuity was 20/20 OU without relative afferent pupillary defect and normal intraocular pressures. Bedside anterior segment examination was normal. Posterior segment examination revealed intraretinal hemorrhages and Roth spots in the posterior pole of the right eye, and two deep well-defined focal white chorioretinal infiltrates and a hemorrhagic pigment epithelium detachment in the temporal quadrant of the left eye. Multimodal imaging was utilized to document these findings and ensure adequate antibiotic therapy. Conclusion: SAB has the potential for poor visual outcomes as well as significant morbidity and mortality. Multimodal imaging of SAB-related chorioretinitis allows for accurate diagnosis as well as assessment of response to antimicrobial therapy.

Retinal blood vessels provide the necessary energy, nutrients and oxygen in order to support visual function and remove harmful particles from blood, thus acting to protect neuronal cells. The homeostasis of the retinal vessels is important for the maintenance of retinal visual function. Neovascularization is the most common cause of blindness in patients with retinopathy. Previous studies have shown that inflammatory mediators are known key regulators in retinopathy, but their causal link has been elusive. Although inflammation is often thought to arise from inflammatory cells like macrophages, neutrophils, and resident microglia, retinal neurons have also been reported to contribute to inflammation, through inflammatory signals, which mediate blood vessel growth. Therefore, it is important to explore the detailed mechanisms of neuroinflammation's effects on retinal neovascularization. This review looks to summarize current research on the relationship between retinal angiogenesis and neuroinflammation in retinopathy, as well as the potential effects of neuroinflammation on retinal neovascularization in different animal models.

We tested younger and older observers' attention and long-term memory functions in a "hybrid search" task, in which observers look through visual displays for instances of any of several types of targets held in memory. Apart from a general slowing, search efficiency did not change with age. In both age groups, reaction times increased linearly with the visual set size and logarithmically with the memory set size, with similar relative costs of increasing load (Experiment 1). We replicated the finding and further showed that performance remained comparable between age groups when familiarity cues were made irrelevant (Experiment 2) and target-context associations were to be retrieved (Experiment 3). Our findings are at variance with theories of cognitive aging that propose age-specific deficits in attention and memory. As hybrid search resembles many real-world searches, our results might be relevant to improve the ecological validity of assessing age-related cognitive decline.

Transcriptional mechanisms that drive angiogenesis and organotypic vascular endothelial cell specialization are poorly understood. Here, we show that retinal endothelial sphingosine 1-phosphate receptors (S1PRs), which restrain vascular endothelial growth factor (VEGF)-induced angiogenesis, spatially restrict expression of JunB, a member of the activator protein 1 (AP-1) family of transcription factors (TFs). Mechanistically, VEGF induces JunB expression at the sprouting vascular front while S1PR-dependent vascular endothelial (VE)-cadherin assembly suppresses JunB expression in the nascent vascular network, thus creating a gradient of this TF. Endothelial-specific JunB knockout mice showed diminished expression of neurovascular guidance genes and attenuated retinal vascular network progression. In addition, endothelial S1PR signaling is required for normal expression of β-catenin-dependent genes such as TCF/LEF1 and ZIC3 TFs, transporters, and junctional proteins. These results show that S1PR signaling restricts JunB function to the expanding vascular front, thus creating an AP-1 gradient and enabling organotypic endothelial cell specialization of the vascular network.

Cannabis is the most prevalent drug in the world and its consumption is growing. Cannabinoid receptors are present in the human central nervous system. Recent studies show evidence of the effects of cannabinoids on the retina, and synthesising the results of these studies may be relevant for ophthalmologists. Thus, this review adopts standardised, systematic review methodology to investigate the effects of exposure to cannabis and components on the retina. We searched five online databases for the combined terms for outcome ("retina") and exposure ("cannabis"). Eligibility of studies were conducted by two independent reviewers, and risk of bias was assessed. We retrieved 495 studies, screened 229 studies, assessed 52 studies for eligibility, and included 16 studies for qualitative analysis. The cannabinoids most frequently investigated were delta-9-tetrahydrocannabinol (THC), abnormal cannabidiol, synthetic cannabinoid, and cannabidiol (CDB). The outcomes most studied were neuroretinal dysfunction, followed by vascular effects. The studies also included investigation of neuroprotective and anti-inflammatory effects and teratogenic effects. This review suggests that cannabinoids may have an important role in retinal processing and function.