Fleur O'Hare

Impaired Complex-I-Linked Respiration and ATP Synthesis in Primary Open-Angle Glaucoma Patient Lymphoblasts

PURPOSE Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes of POAG patients, the authors sought to characterize mitochondrial function in a separate cohort of POAG. METHODS Using similar methodology to that previous applied to Lebers hereditary optic neuropathy (LHON) patients, maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well as cell growth rates in glucose and galactose media, were assessed in transformed lymphocytes from POAG patients (n = 15) and a group of age- and sex-matched controls (n = 15). RESULTS POAG lymphoblasts had significantly lower rates of complex-I-driven ATP synthesis, with preserved complex-II-driven ATP synthesis. Complex-I driven maximal respiration was also significantly decreased in patient cells. Growth in galactose media, where cells are forced to rely on mitochondrial ATP production, revealed no significant differences between the control and POAG cohort. CONCLUSIONS POAG lymphoblasts in the study cohort exhibited a defect in complex-I of the oxidative phosphorylation pathway, leading to decreased rates of respiration and ATP production. Studies in LHON and other diseases have established that lymphocyte oxidative phosphorylation measurement is a reliable indicator of systemic dysfunction of this pathway. While these defects did not impact lymphoblast growth when the cells were forced to rely on oxidative ATP supply, the authors suggest that in the presence of a multitude of cellular stressors as seen in the early stages of POAG, these defects may lead to a bioenergetic crisis in retinal ganglion cells and an increased susceptibility to cell death.

Prevalence of signs and symptoms of ocular surface disease in individuals treated and not treated with glaucoma medication.

Background:  To determine the prevalence of signs and symptoms of ocular surface disease in two hospital‐based cohorts; glaucoma patients and non‐glaucoma patients.

Topical prostaglandin analogues do not affect selective laser trabeculoplasty outcomes.

PurposeTo investigate the effect of topical prostaglandin analogue use on the efficacy of selective laser trabeculoplasty (SLT) intraocular pressure (IOP) lowering in patients with open-angle glaucoma.Patients and MethodsThis retrospective study included 123 consecutive patients who underwent 180° SLT for the first time. Eyes were grouped into those that received prostaglandin analogues before and after SLT (n=74) and those that did not (n=49). The main outcome measure was IOP lowering after SLT. Success was defined as ⩾20% reduction in IOP without further glaucoma intervention.ResultsThere was no significant difference in IOP lowering at 6 months post-laser between the prostaglandin and non-prostaglandin groups (3.9±4.8 vs4.6±3.6 mm Hg, P=0.43). Long-term SLT success rates were also not significantly different between the treatment groups (Kaplan–Meier survival analysis, P=0.68). IOP lowering at 6 months was similar in eyes that received no glaucoma medications, monotherapy with or without a prostaglandin analogue, or combination therapy with or without prostaglandin analogues (P=0.81). Logistic regression analysis showed that various patient characteristics including age, sex, type of glaucoma, previous glaucoma surgery, and other glaucoma risk factors did not predict a successful SLT outcome. However, higher pre-operative IOP was found to predict SLT success (odds ratio=1.12, 95% CI=1.02–1.24, P=0.02).ConclusionThe IOP lowering efficacy of SLT is not influenced by the use of topical prostaglandin analogues.

Auditory processing deficits in individuals with primary open-angle glaucoma

Abstract Objective: The high energy demand of the auditory and visual pathways render these sensory systems prone to diseases that impair mitochondrial function. Primary open-angle glaucoma, a neurodegenerative disease of the optic nerve, has recently been associated with a spectrum of mitochondrial abnormalities. This study sought to investigate auditory processing in individuals with open-angle glaucoma. Design/Study sample: Twenty-seven subjects with open-angle glaucoma underwent electrophysiologic (auditory brainstem response), auditory temporal processing (amplitude modulation detection), and speech perception (monosyllabic words in quiet and background noise) assessment in each ear. A cohort of age, gender and hearing level matched control subjects was also tested. Results: While the majority of glaucoma subjects in this study demonstrated normal auditory function, there were a significant number (6/27 subjects, 22%) who showed abnormal auditory brainstem responses and impaired auditory perception in one or both ears. Conclusions: The finding that a significant proportion of subjects with open-angle glaucoma presented with auditory dysfunction provides evidence of systemic neuronal susceptibility. Affected individuals may suffer significant communication difficulties in everyday listening situations.

Is primary open‐angle glaucoma part of a generalized sensory neurodegeneration? A review of the evidence

Open‐angle glaucoma is an optic neuropathy that has a multifarious aetiological profile. Emerging theories suggest that a group of factors induce optic nerve injury in innately susceptible aging optic nerves. These factors have the potential to impact on the function of other vulnerable neurons within the central nervous system of older patients. Although changes within the visual pathways due to retinal ganglion cell dysfunction and death are well established, research exploring the behaviour of other sensory systems in individuals with glaucoma is limited. This review summarizes what is known about these other non‐visual sensory changes, explores whether glaucoma is in fact part of a global neurodegenerative condition, and suggests areas for future research direction.

Readability of prescription labels and medication recall in a population of tertiary referral glaucoma patients.

Purpose:  To evaluate readability of eye drop labels and accurate recall of prescription instructions in a glaucoma population.

Problem-solving therapy for adults with diabetic retinopathy and diabetes-specific distress: a pilot randomized controlled trial

Objective To provide preliminary evidence for the impact of problem-solving therapy for diabetes (PST-D) in adults with diabetic retinopathy (DR) and diabetes distress. Research design and methods In a pilot randomized controlled trial, 40 participants with DR and diabetes distress were allocated to the PST-D or control groups. Diabetes distress (DDS), depressive symptoms (PHQ-9), self-care activities (SDSCA), and HbA1c were assessed at baseline, and 3 and 6-month follow-ups. Results At the 6-month follow-up, the PST-D group showed significant improvements relative to the control group, in ‘regimen-related distress’ (PST-D: −1.3±1.4; control: −0.4±1.1), depressive symptoms (PST-D: −4.3±6.1; control: −0.3±4.6), and HbA1c (PST-D: −1.2%±1.01; control: 0.2%±1.2%) (all p<0.05). In multiple regression analysis, adjusting for baseline values and sociodemographic factors, PST-D was associated with significant improvement in ‘regimen-related distress’, depressive symptoms, and HbA1c at the 6-month follow-up (p<0.05). Conclusions PST-D is a promising intervention for improving psychological outcomes and glycemic control. A fully powered study is required to confirm these findings and examine mechanisms of change in HbA1c. Trial registration number ACTRN12616001010482; results.

Developing an instrumental activities of daily living tool as part of the low vision assessment of daily activities protocol.

PURPOSE To determine the validity, reliability, and measurement characteristics using factor and Rasch analysis of the Very Low Vision Instrumental Activities of Daily Living (IADL-VLV) in persons with severe vision loss. METHODS From an initial pool of 296 tasks, 25 were shortlisted after conducting a Delphi survey with persons designated legally blind. Using further input from occupational therapy and low-vision professionals, 11 activities were chosen to be pilot tested. Forty legally blind participants (better eye visual acuity < 20/200) underwent clinical assessments and functional tests as well as the 53 IADL tasks related to the 11 activities. The task pool was refined and condensed using factor and Rasch analysis. RESULTS Based on iterative principal component analyses, tasks were grouped together into the following domains: reading signs/information access, signature placement, clothes sorting, shelf search, gesture recognition, clock reading, and table search. A final selection of 23 tasks yielded satisfactory measurement characteristics, differentiated between at least four different levels of IADL performance (person separation of 3.8), and had adequate task difficulty for the tested sample (person mean -0.61). In multivariate analyses, only visual acuity (VA) and percent of remaining visual field (VF) were associated with IADL performance. CONCLUSIONS Using a large item pool, participant, and expert input, as well as factor and Rasch analysis, we designed a valid and reliable assessment to measure vision-related IADL performance in persons with severe vision loss. This assessment tool can be used in clinical sight restoration trials.

Rasch Analysis of the Independent Mobility Questionnaire.

Purpose The Independent Mobility Questionnaire (IMQ) assesses participants’ perceived ability for independent mobility. However, it has not been validated in a severely visually impaired population. The aim of this study was to explore the IMQ’s psychometric properties in participants with severe visual impairment. Methods This was a cross-sectional study of 40 participants with retinitis pigmentosa (better eye visual acuity <20/200 and/or visual field <10%). The key psychometric properties of the IMQ were examined using Rasch analysis, including precision, targeting, and item fit. Construct validity was assessed by testing the correlation between the IMQ and the Mobility and Independence subscale of the Impact of Vision Impairment questionnaire (Pearson correlation coefficient, r). Criterion validity was also assessed. Results The IMQ had excellent precision (Person Separation Index, 3.01) with the capacity to distinguish at least four strata of participant ability, and item difficulty was well targeted to participant ability (difference between mean person and item measures, −0.21). Items 34, 35, 21, and 14 displayed misfit (infit MnSq >1.4); however, given our sample size restrictions, these items were not removed from the analysis. The IMQ had good construct validity (moderate correlation with the Impact of Vision Impairment Mobility subscale, r = 0.595, p < 0.05) but did not demonstrate criterion validity. Conclusions The psychometric properties of the IMQ were promising. Our findings are useful for researchers evaluating the effectiveness of novel treatment technologies on mobility in a severely visually impaired population from the participant’s perspective. However, further validation studies in larger samples are required to confirm our results.

Sociodemographic factors and utilization of eye care services: is there an association with patients presenting to a tertiary referral hospital in acute angle-closure?

Background:  The aim of this study is to examine the relationship between sociodemographic factors and utilization of eye care services in patients presenting in acute angle‐closure (AAC).