Summary Dengue is the second most common mosquito-borne disease affecting human beings. In 2009, WHO endorsed new guidelines that, for the first time, consider neurological manifestations in the clinical case classification for severe dengue. Dengue can manifest with a wide range of neurological features, which have been noted—depending on the clinical setting—in 0·5–21% of patients with dengue admitted to hospital. Furthermore, dengue was identified in 4–47% of admissions with encephalitis-like illness in endemic areas. Neurological complications can be categorised into dengue encephalopathy (eg, caused by hepatic failure or metabolic disorders), encephalitis (caused by direct virus invasion), neuromuscular complications (eg, Guillain-Barre syndrome or transient muscle dysfunctions), and neuro-ophthalmic involvement. However, overlap of these categories is possible. In endemic countries and after travel to these regions, dengue should be considered in patients presenting with fever and acute neurological manifestations.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(13)70150-9.pdf

Neurological complications of dengue virus infection.

Corneal nerves in health and disease

Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS), peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

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Neurological Manifestations of Dengue Infection

Importance Time spent in outdoor activities has decreased owing to home confinement for the coronavirus disease 2019 (COVID-19) pandemic. Concerns have been raised about whether home confinement may have worsened the burden of myopia owing to substantially decreased time spent outdoors and increased screen time at home. Objective To investigate the refractive changes and prevalence of myopia in school-aged children during the COVID-19 home confinement. Design, Setting, and Participants A prospective cross-sectional study using school-based photoscreenings in 123 535 children aged 6 to 13 years from 10 elementary schools in Feicheng, China, was conducted. The study was performed during 6 consecutive years (2015-2020). Data were analyzed in July 2020. Exposures Noncycloplegic photorefraction was examined using a photoscreener device. Main Outcomes and Measures The spherical equivalent refraction was recorded for each child and the prevalence of myopia for each age group during each year was calculated. The mean spherical equivalent refraction and prevalence of myopia were compared between 2020 (after home confinement) and the previous 5 years for each age group. Results Of the 123 535 children included in the study, 64 335 (52.1%) were boys. A total of 194 904 test results (389 808 eyes) were included in the analysis. A substantial myopic shift (approximately −0.3 diopters [D]) was found in the 2020 school-based photoscreenings compared with previous years (2015-2019) for younger children aged 6 (−0.32 D), 7 (−0.28 D), and 8 (−0.29 D) years. The prevalence of myopia in the 2020 photoscreenings was higher than the highest prevalence of myopia within 2015-2019 for children aged 6 (21.5% vs 5.7%), 7 (26.2% vs 16.2%), and 8 (37.2% vs 27.7%) years. The differences in spherical equivalent refraction and the prevalence of myopia between 2020 and previous years were minimal in children aged 9 to 13 years. Conclusions and Relevance Home confinement during the COVID-19 pandemic appeared to be associated with a significant myopic shift for children aged 6 to 8 years according to 2020 school-based photoscreenings. However, numerous limitations warrant caution in the interpretation of these associations, including use of noncycloplegic refractions and lack of orthokeratology history or ocular biometry data. Younger children’s refractive status may be more sensitive to environmental changes than older ages, given the younger children are in a critical period for the development of myopia.

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Progression of Myopia in School-Aged Children After COVID-19 Home Confinement.

Studies in this laboratory have previously shown that hydroxytyrosol, the major antioxidant polyphenol in olives, protects ARPE-19 human retinal pigment epithelial cells from oxidative damage induced by acrolein, an environmental toxin and endogenous end product of lipid oxidation, that occurs at increased levels in age-related macular degeneration lesions. A proposed mechanism for this is that protection by hydroxytyrosol against oxidative stress is conferred by the simultaneous activation of two critically important pathways, viz., induction of phase II detoxifying enzymes and stimulation of mitochondrial biogenesis. Cultured ARPE-19 cells were pretreated with hydroxytyrosol and challenged with acrolein. The protective effects of hydroxytyrosol on key factors of mitochondrial biogenesis and phase II detoxifying enzyme systems were examined. Hydroxytyrosol treatment simultaneously protected against acrolein-induced inhibition of nuclear factor-E2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor coactivator 1 alpha (PPARGC1α) in ARPE-19 cells. The activation of Nrf2 led to activation of phase II detoxifying enzymes, including γ-glutamyl-cysteinyl-ligase, NADPH (nicotinamide adenine dinucleotide phosphate)-quinone-oxidoreductase 1, heme-oxygenase-1, superoxide dismutase, peroxiredoxin and thioredoxin as well as other antioxidant enzymes, while the activation of PPARGC1α led to increased protein expression of mitochondrial transcription factor A, uncoupling protein 2 and mitochondrial complexes. These results suggest that hydroxytyrosol is a potent inducer of phase II detoxifying enzymes and an enhancer of mitochondrial biogenesis. Dietary supplementation of hydroxytyrosol may contribute to eye health by preventing the degeneration of retinal pigment epithelial cells induced by oxidative stress.

Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells

Introduction
In recent years there has been a spurt of peer-reviewed publications on the ophthalmic complications of dengue fever. The authors aim to review the ocular manifestations, utility of relevant diagnostic tests, management, prognosis, and sequelae of dengue-related ocular complications.

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Ophthalmic Complications of Dengue Fever: a Systematic Review

Based on a review of 20 well-documented cases reported in the English literature between 1968 and 2008, herpes zoster ophthalmicus (HZO) may rarely be associated with complete unilateral ophthalmoplegia, defined here as impaired ocular ductions in all 4 directions within 3 months of onset of manifestations of HZO. Ophthalmoplegia occurred equally in immune-competent and immune-incompetent individuals. HZO preceded ophthalmoplegia in 75% by a mean interval of 9.5 days and a range of 2 to 60 days, occurred simultaneously with ophthalmoplegia in 20%, and followed by 2 days the onset of ophthalmoplegia in only 5%. Concurrent conjunctival inflammation, keratitis, or anterior uveitis was present in 90%. Lumbar puncture showed features of aseptic meningitis in 88%, slightly more than the 40%-50% found in patients with HZO without ophthalmoplegia. On orbit/brain imaging, abnormal enlargement of the extraocular muscles was present in 33%, and orbital soft tissue swelling was present in 17%. Enhancement of ocular motor cranial nerves was not reported. Complete or near-complete resolution of ophthalmoplegia occurred in 65% within a range of 2 weeks to 1.5 years (mean 4.4 months). A single autopsy report described granulomatous angiitis of the meninges and large vessels in the anterior cerebral circulation, as well as periaxial infarction in the optic nerve, pons, and medulla but without viral inclusion bodies or antigen. Unsettled issues are whether the pathogenesis is direct viral invasion or an immune reaction to the virus, whether the impaired ocular ductions are based on myopathic or neuropathic injury, whether there are predisposing factors to the combination of HZO and complete ophthalmoplegia, and whether treatment is effective.

Complete unilateral ophthalmoplegia in herpes zoster ophthalmicus.

To report a case series of three patients of optic neuropathy associated with dengue fever. Observational case series. Three patients aged of 19, 31, and 40 years (cases 1, 2, and 3) complained of unilateral blurring of vision within a week of being diagnosed with dengue fever. Their presenting visual acuities were counting fingers in cases 1 and 2, and 6/6 in case 3, with features suggestive of optic neuropathy. Two of the three patients (cases 2 and 3) had bilateral ocular signs. The visual acuity recovered to 6/9 in case 1, worsened to no light perception in case 2, and remained unchanged in case 3. Although spontaneous visual recovery is possible, optic neuropathy associated with dengue fever may result in severe and permanent visual loss.

/pdf/optic-neuropathy-associated-with-dengue-fever-3ena0vhccu.pdf

Optic neuropathy associated with dengue fever.

The management of herpes zoster (HZ) usually involves a multidisciplinary approach aiming to reduce complications and morbidity Patients with herpes zoster ophthalmicus (HZO) are referred to ophthalmologists for prevention or treatment of its potential complications Without prompt detection and treatment, HZO can lead to substantial visual disability In our practice, we usually evaluate patients with HZO for corneal complications such as epithelial, stromal, and disciform keratitis; anterior uveitis; necrotizing retinitis; and cranial nerve palsies in relation to the eye These are acute and usually sight-threatening We recommend oral acyclovir in conjunction with topical 3% acyclovir ointment, lubricants, and steroids for conjunctival, corneal, and uveal inflammation associated with HZO Persistent vasculitis and neuritis may result in chronic ocular complications, the most important of which are neurotrophic keratitis, mucus plaque keratitis, and lipid degeneration of corneal scars Postherpetic complications, especially postherpetic neuralgia (PHN), are observed in well over half of patients with HZO The severe, debilitating, chronic pain of PHN is treated locally with cold compresses and lidocaine cream (5%) These patients also receive systemic treatment with NSAIDs, and our medical colleagues cooperate in managing their depression and excruciating pain Pain is the predominant symptom in all phases of HZ disease, being reported by up to 90% of patients Ocular surgery for HZO-related complications is performed only after adequately stabilizing pre-existing ocular inflammation, raised intraocular pressure, dry eye, neurotrophic keratitis, and lagophthalmos Cranial nerve palsies are common and most often involve the facial nerve, although palsy of the oculomotor, trochlear, and abducens nerves may occur in isolation or (rarely) simultaneously In our setting, complete ophthalmoplegia is seen more often than isolated palsies, but recovery is usually complete Vasculitis within the orbital apex (orbital apex syndrome) or brainstem dysfunction is postulated to be the cause of cranial nerve palsies A vaccine of a lyophilized preparation of the oka strain of live, attenuated varicella-zoster virus is suggested for patients who are at risk of developing HZ and has been shown to boost immunity against HZ virus in older patients

Herpes Zoster Ophthalmicus

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Context: The Indian subcontinent is one of the most populous regions in the world. Given the projected rapid population growth and ageing of the population, age-related macular degeneration (AMD) is likely to emerge as a major public health threat in the near future. However, existing literature on AMD in the region is scarce.



Methods:  This paper reviews the epidemiology and risk factors of AMD in the Indian subcontinent.



Results:  Data on AMD in India show prevalences ranging from 1.8% to 4.7%. Blindness prevalence studies in Pakistan, Bangladesh and Nepal have also reported rates of 2.1% to 8.7% for all blindness attributable to AMD. Age-related macular degeneration is therefore a significant cause of visual morbidity in these countries. To date, no reliable epidemiological data on AMD or blindness have been published for Sri Lanka, Afghanistan, Maldives or Bhutan.



Conclusions:  The prevalence of AMD in the region is likely to follow a trend similar to that seen in the developed world in the coming years. Eye care policies should therefore make provisions for this chronic age-related eye disease. In addition, there is an urgent need for more data on the epidemiology of AMD in the Indian subcontinent.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1755-3768.2008.01376.x

Srinivasan Sanjay

Papers

Ophthalmic Complications of Dengue Fever: a Systematic Review

Complete unilateral ophthalmoplegia in herpes zoster ophthalmicus.

Optic neuropathy associated with dengue fever.

Herpes Zoster Ophthalmicus

The epidemiology of age-related macular degeneration in the Indian subcontinent