Impact of ocular disease on circadian rhythms and brain connectivity

Investigation into the impact of ocular disease on sleep and mood has shown that in humans eyes have an important role, and that absence of eyes or interference with light reaching the retina can have deleterious effects. Light is the main zeitgeber ‘time-giver’ used by most species for the regulation of circadian rhythms and is detected by rods, cones and photosensitive retinal ganglion cells (pRGCs) in mammals. The aims of this research project were to investigate this from three different perspectives. Three prospective studies were undertaken. The first, studied the impact of ocular disease on the sleep/wake cycle in diabetic retinopathy (DR) and in bilateral anophthalmia. There was no significant difference found between the severity of DR and global sleep scores, however the acquired anophthalmic groups have significantly raised global sleep scores compared to controls and the congenital anophthalmic group. Both anophthalmic groups had varying sleep/wake cycles on their actograms depending on the lifestyle (independent of the urinary melatonin). All the anophthalmic participants showed a non 24 hour sleep-wake rhythm disorder after melatonin profiling. The second study investigates the evidence for the presence of extraocular circadian photoreceptors (EOCP) in participants with anophthalmia and sighted controls. Changes in brain activity using a functional MRI scan was assessed, when a bright white light is shining in different locations. This study did not reveal any evidence of EOCP.Finally, structural brain MRI differences in anophthalmic groups were investigated. While similar changes in structural reorganisation occur in all anophthalmic groups in the occipital cortex, the acquired anophthalmic groups show an inverse relation with the time since becoming anophthalmic and the volume of optic radiation and optic nerve volume. The acquired anophthalmic group did not show increase in hippocampal volume (memory areas) or in the precuneus (spatial navigation) contrast to the congenital anophthalmic groups

Lowering the limit : reducing the CD4 T-cell threshold for ophthalmic screening in patients with HIV in an ethnically diverse UK population

BACKGROUND: Before highly active antiretroviral therapy, cytomegalovirus (CMV) retinitis was a major threat to vision in individuals with HIV. We investigate whether ophthalmic screening of asymptomatic HIV patients still has value in the highly active antiretroviral therapy era and consider CD4 thresholds in line with the world literature and UK experience. METHODS: A retrospective chart review was conducted of all patients seen by the HIV Ophthalmic Service of a UK university hospital both before (2007–2008) and after (2011–2012) introduction of a threshold of CD4 lower than 100 cells/mm(3). Data collected included CMV and HIV RNA load, CD4 cell counts and CD4 percentage, CMV-immunoglobulin G status, ocular symptoms, and evidence of HIV-related ocular disease. RESULTS: In total, 54 patients were referred to the HIV ophthalmic service. Three patients failed to attend, resulting in complete data for 51 patients (n=24 for 2007–2008; n=27 for 2011–2012). Seven patients had ophthalmic manifestations of their HIV; these cases had lower CD4 counts than those with normal examinations (median [interquartile range], 9 [7–80] versus 175 [44–394]; P=0.0039; Mann–Whitney test). Six cases had HIV retinopathy without sight loss; one case had sight-threatening CMV retinitis associated with a CD4 count of 6 cells/mm(3). CONCLUSION: Before 2008, our practice was to screen all asymptomatic patients with CD4 counts lower than 200 cells/mm(3). Screening asymptomatic patients with CD4 counts below 100 cells/mm(3) was not associated with any missed or late-presenting cases of CMV retinitis in our HIV population

Treating Diabetic Macular Oedema (DMO): real world UK clinical outcomes for the 0.19mg Fluocinolone Acetonide intravitreal implant (Iluvien™) at 2 years

Abstract Background To compare visual function and structural improvements in pseudophakic eyes with diabetic macular oedema (DMO) treated with the 0.19mg Fluocinolone Acetonide (FAc) intravitreal implant (IluvienTM) in a ‘real world’ setting. Methods A single centre retrospective evaluation of patients with DMO unresponsive to conventional treatment treated with the FAc implant according to UK guidelines. Primary efficacy endpoint was best corrected visual acuity (BCVA); secondary endpoints included optical coherence tomography evaluations of the macula (a) central retinal and (b) peak macular thickness collected at annual time points. Primary safety endpoint was new rise in IOP >27mmHg or glaucoma surgery. Patients with <1 year follow-up were excluded. Results Twenty-nine eyes were included, with mean(SD) follow up of 792(270) days. Improvement in BCVA and reduction in macular oedema was noted at all timepoints. Mean improvement in BCVA from baseline was 6 ETDRS letters at year 1(n=29), 6.5L at year 2(n=22) and 11L at year 3(n=6). Mean central retinal thickness at baseline was 451 microns, 337 microns at year 1, 342 microns at year 2 and 314 microns at year 3. Two eyes required IOP-lowering drops post implant. Supplementary treatment for persistence or recurrence of DMO was necessary in 18 eyes over the total study period of 3 years with mean time to supplementary treatment being 12 months. Conclusions Our evaluation of the 0.19mg FAc implant delivered in a real-world setting, provides additional evidence that it is effective and safe in the treatment of patients with DMO, and can provide sustained benefit for patients with previously refractory disease

Correction to: Iluvien™ (Fluocinolone Acetonide 0.19 mg Intravitreal Implant) in the Treatment of Diabetic Macular Edema: A Review.

This article was originally published with the copyright: the author(s) 2018, CC-BY-NC. However, the license should be the author(s) 2018, CC-BY