Michelle L. Baker

Retinal microvasculature in acute lacunar stroke: a cross-sectional study

BACKGROUNDnLacunar stroke accounts for a quarter of cases of acute ischaemic stroke; however, its underlying pathophysiology remains unclear. Our aim was to establish whether there is an association between changes in the retinal microvasculature and lacunar stroke that might provide clues to the pathology of cerebral small vessel disease.nnnMETHODSnIn this cross-sectional study, we recruited patients who presented with acute stroke at three centres in two countries (Sydney and Melbourne, Australia, and Singapore). Each patient had standardised clinical assessments, retinal photography, and CT or MRI of the brain. Changes in the retinal microvasculature were assessed from retinal photographs by graders who were masked to the patients clinical details. Lacunar stroke was diagnosed according to a modified version of the TOAST criteria (Treatment of Acute Stroke Trial) or the OCSP criteria (Oxfordshire Community Stroke Project) and by MRI findings.nnnFINDINGSnWe recruited 1321 patients aged 19 to 94 years with acute ischaemic stroke; 410 (31%) had lacunar stroke. Patients with acute lacunar stroke were no more likely to have hypertension (p=0.12), diabetes (p=0.51), or hypercholesterolaemia (p=0.91) than were patients with other types of ischaemic stroke. However, patients with lacunar stroke were more likely to have retinal microvessel signs, particularly when stroke subtype was confirmed using diffusion-weighted MRI, than were patients with other stroke subtypes. After adjustment for age, sex, study site, smoking history, hypertension, and diabetes, the patients with lacunar stroke were more likely than those with other stroke subtypes to have microvessel signs, and when stroke subtype was confirmed by diffusion-weighted MRI the odds ratios were: 3.55 (95% CI 1.77-7.12) for focal arteriolar narrowing; 1.96 (1.19-3.24) for arteriovenous nipping; 2.32 (1.42-3.79) for enhanced light reflex of the arteriolar wall; 1.33 (0.74-2.41) for generalised retinal arteriolar narrowing; 1.45 (0.84-2.51) for small retinal arteriole:venule ratio; and 1.35 (0.80-2.26) for retinal venular widening.nnnINTERPRETATIONnOur findings suggest that acute lacunar stroke is a manifestation of non-atherothrombotic occlusive small vessel disease, which might have implications for the prevention and treatment of this stroke subtype.nnnFUNDINGnNational Health and Medical Research Council of Australia; National Medical Research Council of Singapore; Scottish Funding Council; New South Wales Health.

Retinal Microvascular Signs, Cognitive Function, and Dementia in Older Persons The Cardiovascular Health Study

Background and Purpose— Cerebral microvascular disease may be a risk factor for the development of dementia in elderly persons. We describe the association of retinal microvascular signs with cognitive function and dementia among older individuals. Methods— In the population-based Cardiovascular Health Study, 2211 persons aged 69 to 97 years at recruitment had retinal photography. Photographs were evaluated for retinopathy (eg, microaneurysms, retinal hemorrhages), focal arteriolar narrowing, arteriovenous nicking, and retinal arteriolar and venular caliber. Cognitive status was determined from the Digit-Symbol Substitution Test and Modified Mini-Mental State Examination. Participants were also further evaluated for the presence of dementia with detailed neuropsychological testing. Persons with a prior stroke or taking antipsychotic or antidepressant medications were excluded. Results— After adjusting for age, gender, race, field center, education level, internal carotid intima-media thickness, body mass index, hypertension, diabetes, and cigarette smoking status, persons with retinopathy had lower mean Digit-Symbol Substitution Test scores but not Modified Mini-Mental State Examination than those without retinopathy (39 versus 41, P=0.002). In hypertensive persons, retinopathy (multivariable-adjusted OR, 2.10; 95% CI, 1.04 to 4.24) and focal arteriolar narrowing (OR, 3.02; 95% CI, 1.51 to 6.02) were associated with dementia. These associations were not present in individuals without hypertension. Conclusions— In older persons, our study shows a modest cross-sectional association between retinopathy signs with poorer cognitive function and, in persons with hypertension, with dementia. These data support a possible role of cerebral microvascular disease in the pathogenesis of impaired cognitive function and dementia in older hypertensive persons.

Retinal fractals and acute lacunar stroke

This study aimed to determine whether retinal fractal dimension, a quantitative measure of microvascular branching complexity and density, is associated with lacunar stroke. A total of 392 patients presenting with acute ischemic stroke had retinal fractal dimension measured from digital photographs, and lacunar infarct ascertained from brain imaging. After adjusting for age, gender, and vascular risk factors, higher retinal fractal dimension (highest vs lowest quartile and per standard deviation increase) was independently and positively associated with lacunar stroke (odds ratio [OR], 4.27; 95% confidence interval [CI], 1.49–12.17 and OR, 1.85; 95% CI, 1.20–2.84, respectively). Increased retinal microvascular complexity and density is associated with lacunar stroke. ANN NEUROL 2010;68:107–111

Early Age-Related Macular Degeneration, Cognitive Function and Dementia: The Cardiovascular Health Study

OBJECTIVEnTo describe the association of cognitive function and dementia with early age-related macular degeneration (AMD) in older individuals.nnnMETHODSnThis population-based study included 2,088 persons aged 69 to 97 years who participated in the Cardiovascular Health Study. The AMD was assessed from retinal photographs based on a modified Wisconsin AMD grading system. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST) and the Modified Mini-Mental State Examination. Participants were also evaluated for dementia using detailed neuropsychological testing.nnnRESULTSnAfter controlling for age, sex, race, and study center, persons with low DSST scores (lowest quartile of scores, < or =30) were more likely to have early AMD (odds ratio, 1.38; 95% confidence interval, 1.03-1.85) than were persons with higher DSST scores. In analyses further controlling for education, systolic blood pressure, total cholesterol level, diabetes mellitus, smoking status, and apolipoprotein E genotype, this association was stronger (odds ratio, 2.00; 95% confidence interval, 1.29-3.10). There was no association of low Modified Mini-Mental State Examination scores, dementia, or Alzheimer disease with early AMD.nnnCONCLUSIONSnIn this older population, cognitive impairment may share common age-related pathogenesis and risk factors with early AMD.

Retinal Microvascular Signs May Provide Clues to the Underlying Vasculopathy in Patients With Deep Intracerebral Hemorrhage

Background and Purpose— Deep intracerebral hemorrhage (ICH) and lacunar infarcts are the result of small vessel disease, whereas nonlacunar infarcts are often caused by large artery atherosclerosis or cardiac embolism. We hypothesized that patients with deep ICH and lacunar infarcts have similar retinal microvascular signs and that these differ from those seen in patients with nonlacunar infarcts. Methods— We studied patients with acute stroke and classified their stroke as deep ICH, lacunar infarction, or nonlacunar infarction. In a masked fashion we assessed retinal photographs for quantitative and qualitative evidence of microvascular damage. Results— We recruited 630 patients (51 had deep ICH, 93 had lacunar infarction, and 486 had nonlacunar infarction). Patients with deep ICH were more likely than those with nonlacunar infarcts to have severe focal narrowing of the retinal arterioles (OR, 3.7), severe arteriovenous nicking (OR, 2.6), and quantitatively narrower retinal arterioles and wider retinal venules. Retinal microvascular signs were similar in patients with deep ICH and lacunar infarction. Conclusions— Patients with deep ICH and lacunar infarcts are more likely than patients with nonlacunar infarcts to have signs indicating hypertensive damage in the retinal arteriolar wall.

Differential Associations of Cortical and Subcortical Cerebral Atrophy With Retinal Vascular Signs in Patients With Acute Stroke

Background and Purpose— The relationship of cortical and subcortical cerebral atrophy to cerebral microvascular disease is unclear. We aimed to assess the associations of retinal vascular signs with cortical and subcortical atrophy in patients with acute stroke. Methods— In the Multi-Centre Retinal Stroke Study, 1360 patients with acute stroke admitted to 2 Australian and 1 Singaporean tertiary hospital during 2005 to 2007 underwent neuroimaging and retinal photography. Cortical and subcortical cerebral atrophy were graded based on standard CT scans. A masked assessment of retinal photographs identified focal retinal vascular signs, including retinopathy and retinal arteriolar wall signs (ie, focal arteriolar narrowing, arteriovenous nicking, arteriolar wall light reflex) and measured quantitative signs (retinal arteriolar and venular caliber). Results— After adjusting for age, gender, study site, hypertension, hypercholesterolemia, diabetes, and smoking status, none of the retinal vascular signs assessed were associated with cortical atrophy, whereas retinopathy (OR, 1.9; CI, 1.2 to 3.0) and enhanced arteriolar light reflex (OR, 2.0; CI, 1.2 to 3.2) were significantly associated with subcortical atrophy. Conclusion— Our finding that certain retinal vascular signs are associated with subcortical but not cortical atrophy, suggests a differential pathophysiology between these 2 cerebral atrophy subtypes and a potential role for small vessel disease underlying subcortical cerebral atrophy.

Terson's syndrome in spontaneous spinal subarachnoid haemorrhage.

This paper is a case report of Tersons Syndrome (TS) in spontaneous spinal subarachnoid haemorrhage (SAH). A 66-year-old woman with acute onset of severe back pain was transferred to our institution for management of her sciatica. The presence of an intraretinal haemorrhage alerted us to consider intracranial SAH, but investigations showed no intracranial source. Eventually, the patient was diagnosed with a thoracic spinal SAH. The patients symptoms gradually improved with conservative management but within 1 month she had a recurrence. A spinal and CT angiogram did not elicit the aetiology. The diagnosis of spontaneous spinal SAH can be difficult. The recognition of TS has important prognostic implications, often heralding subarachnoid rebleeding. Fundoscopic examination appears mandatory as a tool for diagnosis and regular non-invasive monitoring of patients with SAH.

Differing associations of white matter lesions and lacunar infarction with retinal microvascular signs

Background White matter lesions (WML) and lacunar infarcts (LI) are believed to have microvascular etiologies but the exact microvascular changes occurring in each is unclear. Aim Using the retina as a proxy, we assessed retinal microvascular changes in WML and LI. Methods We prospectively recruited 1211 acute stroke patients. Four subgroups were identified from neuroimaging: WML alone, LI alone, both WML and LI, neither WML nor LI. Masked retinal photographs identified retinopathy and retinal arteriolar wall signs and measured retinal vascular caliber. Results Compared with 448 controls with neither WML nor LI, 384 patients with only WML were more likely to have retinopathy [odds ratio (OR) 1·5, 95% confidence interval (CI) 1·1 to 2·1] and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·1 to 2·3); 200 patients with only LI were more likely to have arteriolar narrowing (OR 1·6, 95% CI 1·1 to 2·3) and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·0 to 2·4); and 179 patients with both WML and LI were more likely to have arteriovenous nicking (OR 1·7, 95% CI 1·1 to 2·6), enhanced arteriolar light reflex (OR 2·0, 95% CI 1·3 to 3·2) and wider venules (OR 2·3, 95% CI 1·4 to 3·6). All analyses were adjusted for age, gender, study site and cardiovascular risk factors. Conclusion Both WML and LI were associated with retinal microvascular signs, supporting a microvascular etiology. Differing patterns of association suggest different mechanisms may predominate, e.g. greater endothelial permeability in WML, and ischemia associated with arteriolar wall disease in LI.

Immune recovery uveitis in an HIV-negative individual†

Immune recovery uveitis (IRU) is an intraocular inflammatory disorder originally described in individuals with human immunodeficiency virus (HIV) and inactive cytomegalovirus retinitis following highly active antiretroviral therapy. Although relatively common in individuals with acquired immune deficiency syndrome in the United States it is an extremely uncommon presentation in Australia. IRU also occurs in iatrogenically immunosuppressed individuals with a similar incidence to HIV‐infected individuals. We report one case of IRU in an HIV‐negative individual following a volunteer unrelated donor allogeneic stem cell transplant for non‐Hodgkins lymphoma. In the context of tapering the immunosuppression the patient developed bilateral IRU, consisting of panuveitis and macular oedema. The visual acuity (VA) at presentation of IRU was limited to counting fingers bilaterally. The IRU resolved with the re‐intensification of the immunosuppression. VA restored to right 6/18 and left 6/12.

Ocular trauma in the Solomon Islands.

Following eye trauma in Papua New Guinea, there is frequently a poor visual outcome with 60% having a visual acuity of less than 6/60 in the injured eye. The factors predisposing the Solomon Islanders to poor visual outcome after eye trauma also exist elsewhere in the Pacific. There is often a delay in obtaining ophthalmic care: primary surgical repair for penetrating trauma and the timely application of intensive appropriate topical ocular antibiotics. The reasons for this delay include a lack of community eye health awareness (with patients often presenting when the vision has deteriorated), long distances on foot or by canoe to primary healthcare centres, inconsistent and expensive transport systems and lack of appropriate medication at many primary, district and even provincial clinics. Also there is a common fear of hospitals and faith in traditional health workers (THWs). After eye injuries, most patients admit to self-medicating with substances such as the skin of the betel nut, freshly squeezed plant juice or breast milk. Breast milk, although initially sterile is sticky, attracts flies and provides a media for microbial growth. Others consult THWs, believing their ‘kastom meresin’ is more effective. However, traditional eye medicines have an unknown content, concentration, pH and are non-sterile. Other factors that may predispose the eye to infection are the faecal contamination of the ocean surrounding most coastal villages, compromised personal hygiene due to the shortage of running water and the humid climate promoting fungal infection. Thylefors argued that in the developing world superficial corneal injury, which occurs as a result of agricultural work, often leads to rapidly progressive corneal ulceration and subsequent visual loss and has been overlooked as a worldwide cause of monocular blindness. Corneal opacity secondary to trauma has been termed the ‘silent epidemic’ and corneal opacity is the source of 39–70% of monocular blindness worldwide. Indeed a report by the World Health Organization in 2002 lists corneal opacity as the second major cause of blindness in Tonga. However, Tonga and Vanuatu were the only two countries with available data from the Pacific from 1991 and 1989, respectively. Considering the importance of corneal scarring, there are few studies evaluating the aetiological factors predisposing a population to corneal infection secondary to trauma. Upadhyay et al. reported in Nepal if trivial corneal abrasions were treated within 18 h of injury with 1% chloramphenicol 96% healed without developing an ulcer. However, 28.6% developed a corneal ulcer if the treatment was delayed 25–48 h. Furthermore, as public health programmes have become more effective in reducing the prevalence of the traditional causes of corneal blindness, such as trachoma, keratomalacia and leprosy, ocular trauma has become relatively more important. Moreover, there have been no studies in the Pacific to determine if diabetes has an influence on the incidence of infection, or causes delay in healing after ocular trauma. From previous studies the importance of early intervention in ocular trauma seems to be crucial. Therefore the role of the priOcular trauma in the Solomon Islands