Study methodology and diabetes control in patients from the non-English diabetes management project (NEDMP).

BACKGROUND: To describe the clinical characteristics of non-English speaking patients from the Diabetes Management Project (NEDMP), and compare their diabetes management and severity of diabetic retinopathy (DR) with the English-speaking DMP sample (EDMP). DESIGN: A prospective study was conducted on non-English speaking adults with diabetes who attended the Royal Victorian Eye and Ear Hospital. PARTICIPANTS: 136 (90.1%) non-English speaking adults were assessed, with a mean age of 72.2 years (range: 50-88 years); 74 (54.4%) were male. METHODS: Participants completed interviewer-administered questionnaires and underwent visual acuity, fundus photography, optical coherence tomography, biochemistry and anthropometric measurements. The EDMP assessed 609 patients in 2009 using a similar protocol. MAIN OUTCOME MEASURES: Type and duration of diabetes, diabetes control and diabetic retinopathy. RESULTS: A total of 127 (93.4%) and 8 (5.9%) participants reported having type 2 and type 1 diabetes, respectively, with a median (IQR) duration of 17 (14) years. The proportion of patients with poor diabetes control (HbA1c ≥ 7%) in the NEDMP was similar to the EDMP (64.0% and 68.2%, respectively; P = 0.411). A significantly higher proportion of patients with DR in the NEDMP were found to have poor diabetes control (HbA1c ≥ 7%) compared to those without DR (80.9% vs. 50.0%, P = 0.003). Almost two-thirds of NEDMP patients (74/118) had DR and 23% (27/115) had diabetic macular edema. The prevalence of DR was similar between the NEDMP and EDMP studies, ranging from 25-30% and 28-29%. CONCLUSIONS: The clinical characteristics, diabetes control, and DR severity of English and non-English-speaking patients were similar. The high proportion of poor diabetes management in non-English speaking patients with DR suggests educational and behavioural interventions to improve glycaemic control are warranted.

An acute intraocular pressure challenge to assess retinal ganglion cell injury and recovery in the mouse.

We describe a model of acute intraocular pressure (IOP) elevation in the mouse eye that induces reversible loss of inner retinal function associated with oxidative stress, glial cell activation and minimal loss of retinal ganglion cell (RGC) number. Young healthy mouse eyes recover inner retinal function within 7-days but more persistent functional loss is seen in older mice. Manipulation of diet and exercise further modify RGC recovery demonstrating the utility of this injury model for investigating lifestyle and therapeutic interventions. We believe that systematic investigation into the characteristics and determinants of RGC recovery following an IOP challenge will shed light on processes that govern RGC vulnerability in the early stages of glaucoma.

Prevalence and related factors of myopic retinopathy - a hospital-based cross-section study in Vietnam.

CLINICAL RELEVANCE: Myopia prevention and anti-myopia treatment is of great importance in South East Asia. BACKGROUND: To evaluate the prevalence and related factors of myopic retinopathy in Vietnam. METHODS: A cross-sectional study was conducted on 168 eyes of 88 patients with high myopia presenting to the Refraction Department of Vietnam National Eye Hospital. Inclusion criteria were high myopia (≤-6.00D with cycloplegic retinoscopy). Consecutive presenting patients recruited between January 2020 and August 2020 consented to participate. RESULTS: Participant age range was 12-47 years. Peripapillary atrophy was present in 70.2% of participants, most commonly atrophy of one-quarter of the disc (38.7%). Central retinal changes were present in 66.1% of participants, subclassified as tessellated fundus in 60.7%, diffuse chorioretinal atrophy in 4.2% and patchy chorioretinal atrophy in 1.2%. Peripheral retinal lesions were present in 43.5% of participants, consisting of white-without-pressure in 32.1%, lattice degeneration in 16.1%, snail track degeneration in 4.2% and microcystoid degeneration in 1.2%. Myopia ≤-8.00D and axial length ≥26.5 mm were associated with additional risk of posterior ocular complications. Furthermore, age ≥19 years increased risk of central myopic retinopathy and ≥10 years since initial myopia diagnosis increased the risk of peripapillary atrophy and central retinal changes. Other factors such as the age of onset of myopia and family myopia history did not appear to alter the risk of peripheral retina damage. CONCLUSIONS: Retinal disorders were common in Vietnamese people with high myopia. Within the current cohort with high myopia, myopia ≤-8.00D and axial length ≥26.5 mm were associated with a significant further elevation of risk.

Post-receptoral contributions to the rat scotopic electroretinogram a-wave.

The electroretinogram is a widely used objective measure of visual function. The best characterised feature of the full-field dark-adapted flash ERG, is the earliest corneal negativity, the a-wave, which primarily reflects photoreceptoral responses. However, recent studies in humans and primates show that there are post-receptoral contributions to the a-wave. It is not clear if such contributions exist in the rat a-wave. We consider this issue in the rat a-wave, using intravitreal application of pharmacological agents that isolate post-receptoral ON-pathways and OFF-pathways. In anaesthetised adult long Evans rats, we show that the ON-pathway (2-amino-4-phosphonobutyric acid, APB sensitive) makes negligible contribution to the a-wave. In contrast, CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) or PDA (cis-piperidine-2,3-dicarboxylic acid) sensitive mechanisms modify the a-wave in two ways. First, for bright luminous energies, OFF-pathway inhibition (CNQX or PDA) results in a 22% reduction to the early phase of the leading edge of the a-wave up to 14 ms. Second, OFF-pathway inhibition removed a corneal negativity that resides between the a-wave trough and the b-wave onset.

Flicker perimetry losses in age-related macular degeneration.

PURPOSE: To compare static and flicker perimetry outcomes in patients with early age-related macular degeneration (AMD). METHODS: Perimetry was performed in the central visual field of one eye of each of 25 patients with good visual acuity (> 6/12) and early AMD using static and flickering targets. These results were compared with data obtained from a single eye of 34 age-matched control subjects, 33 of whom were retested at 1 to 3 months after their initial visits. RESULTS: In all cases, patients with early AMD had greater mean defects for flickering than static targets, returning a significantly larger group average in response to flicker (4.3 +/- 0.6 dB) than to static (1.8 +/- 0.6 dB; P < 0.005). Greater pattern defect losses were also present in AMD-affected eyes with flicker compared with static perimetry (P < 0.02). These give a higher diagnostic sensitivity for flicker (68% vs. 42%, P < 0.05) at 90% specificity. Sensitivity can be increased to 84% +/- 6% (specificity 92% +/- 4%) if the criterion for failure is a more than 10-dB loss in the foveal region (1 degrees -3 degrees ). CONCLUSIONS: Flickering targets expose foveal deficits in early AMD better than do static targets. Flicker perimetry is an easy, short procedure that may be useful for monitoring the progression of AMD.

Sustained and Transient Contributions to the Rat Dark-Adapted Electroretinogram b-Wave.

The most dominant feature of the electroretinogram, the b-wave, is thought to reflect ON-bipolar cell responses. However, a number of studies suggest that the b-wave is made up of several components. We consider the composition of the rat b-wave by subtracting corneal negative components obtained using intravitreal application of pharmacological agents to remove postreceptoral responses. By analyzing the intensity-response characteristic of the PII across a range of fixed times during and after a light step, we find that the rat isolated PII has 2 components. The first has fast rise and decay characteristics with a low sensitivity to light. GABAc-mediated inhibitory pathways enhance this transient-ON component to manifest increased and deceased sensitivity to light at shorter (<160 ms) and longer times, respectively. The second component has slower temporal characteristics but is more sensitive to light. GABAc-mediated inhibition enhances this sustained-ON component but has little effect on its sensitivity to light. After stimulus offset, both transient and sustained components return to baseline, and a long latency sustained positive component becomes apparent. The light sensitivities of transient-ON and sustained-OFF components are consistent with activity arising from cone ON- and OFF-bipolar cells, whereas the sustained-ON component is likely to arise from rod bipolar cells.

Conscious wireless electroretinogram and visual evoked potentials in rats.

The electroretinogram (ERG, retina) and visual evoked potential (VEP, brain) are widely used in vivo tools assaying the integrity of the visual pathway. Current recordings in preclinical models are conducted under anesthesia, which alters neural physiology and contaminates responses. We describe a conscious wireless ERG and VEP recording platform in rats. Using a novel surgical technique to chronically implant electrodes subconjunctivally on the eye and epidurally over the visual cortex, we are able to record stable and repeatable conscious ERG and VEP signals over at least 1 month. We show that the use of anaesthetics, necessary for conventional ERG and VEP measurements, alters electrophysiology recordings. Conscious visual electrophysiology improves the viability of longitudinal studies by eliminating complications associated with repeated anaesthesia. It will also enable uncontaminated assessment of drug effects, allowing the eye to be used as an effective biomarker of the central nervous system.

Adaptation mechanisms, eccentricity profiles, and clinical implementation of red-on-white perimetry.

PURPOSE: To determine the visual adaptation and retinal eccentricity profiles for red flickering and static test stimuli and report a clinical implementation of these stimuli in visual perimetry. METHODS: The adaptation profile for red-on-white perimetry stimuli was measured using a threshold vs. intensity (TvI) paradigm at 0 degree and 12 degrees eccentricity and by comparing the eccentricity-related sensitivity change for red and white, static, and flickering targets in young normal trichromats (n = 5) and a group of dichromats (n = 5). A group of older normal control observers (n = 30) were tested and retinal disease was evaluated in persons having age-related maculopathy (n = 35) and diabetes (n = 12). RESULTS: Adaptation and eccentricity profiles indicate red static and flickering targets are detected by two mechanisms in the paramacular region, and a single mechanism for >5 degrees eccentricity. The group data for the older normal observers has a high level of inter-observer variability with a generalized reduction in sensitivity across the entire visual field. Group data for the participants with age-related maculopathy show reduced sensitivities that were pronounced in the central retina. The group data for the diabetic observers showed sensitivities that were reduced at all eccentricities. The disease-related sensitivity decline was more apparent with red than white stimuli. CONCLUSIONS: The adaptation profile and change in sensitivity with retinal eccentricity for the red-on-white perimetric stimuli are consistent with two detection processes. In the macula, the putative detection mechanism is color-opponent with static targets and non-opponent with flickering targets. At peripheral field locations, the putative detection mechanism is non-opponent for both static and flicker targets. The long-wavelength stimuli are less affected by the preretinal absorption common to aging. Red-on-white static and flicker perimetry may be useful for monitoring retinal disease, revealing greater abnormalities compared with conventional white-on-white perimetry, especially in the macula where two detection mechanisms are found.