Electronegative electroretinogram in the modern multimodal imaging era.

BACKGROUND: The electronegative electroretinogram (ERG) reflecting inner retinal dysfunction can assist as a diagnostic tool to determine the anatomical location in eye disease. The aim of this study is to determine the frequency and aetiology of electronegative ERG in a tertiary ophthalmology centre and to develop a clinical algorithm to assist patient management. METHODS: Retrospective review of ERGs performed at the Save Sight Institute from January 2011 to December 2020. ERGs were performed according to ISCEV standard. The b:a ratio was analysed in dark adapted (DA) 3.0 or 12.0 recordings. Patients with ratio of ≤1.0 were included. RESULTS: A total of 4421 patients had ERGs performed during study period, of which 139 patients (3.1%) had electronegative ERG. The electronegative ERG patients' median age at referral time was 37 (0.7-90.6) years. The causative aetiologies were photoreceptor dystrophy (48, 34.5%), Congenital Stationary Night Blindness (CSNB) (33, 23.7%), retinal ischemia (18, 12.9%), retinoschisis (15, 10.8%), paraneoplastic autoimmune retinopathy (PAIR) and nonPAIR (14, 10.1%), batten disease (4, 2.9%), and inflammatory retinopathy (4, 2.9%). There were three patients with an unclassified diagnosis. Thirty-two patients (23%) had good vision and a normal fundus appearance. Eleven patients (7.9%) had good vision and normal results in all multimodal imaging. CONCLUSIONS: The frequency of electronegative ERG in our referral centre was 3.1% with photoreceptor dystrophy as the main aetiology. A significant number of the cases had good vision with normal fundus or normal multimodal imaging. This further highlights the value of an ERG in this modern multimodal imaging era.

Biomarkers in Usher syndrome: ultra-widefield fundus autofluorescence and optical coherence tomography findings and their correlation with visual acuity and electrophysiology findings.

PURPOSE: To investigate the functional and structural biomarkers and their correlation with Usher syndrome (USH). METHODS: Medical records, imaging and electrophysiology test results of USH patients attending the Save Sight Institute between 2012 and 2017 were reviewed. Best corrected visual acuity (BCVA), ultra-widefield autofluorescence (UW-FAF), spectral-domain optical coherence tomography (SD-OCT), full-field electroretinogram and pattern electroretinogram (pERG) were performed. SD-OCT scans assessed central macular thickness (CMT), greatest linear diameter of preserved outer retinal layers-macular island (MI) and presence of cystoid macular edema (CME). UW-FAF images were qualitatively graded to identify hypo/hyperfluorescence patterns in the peripheral fundus. RESULTS: Thirty-six eyes from 18 subjects were included. Mean BCVA was 0.22 ± 0.3 LogMAR. MI extent was significantly associated with better vision (ß = - 0.175 per 1000 µm; R2 = 0.487; P = 0.002; Fig. 4). A higher pERG P50 was associated with a larger macular island (ß = 782 per µV; R2 = 0.238; P = 0.025), while a higher pERG N95 was associated with a smaller macular island (ß = - 499 per µV; R2 = 0.219; P = 0.030). Mean CMT was 271 ± 35 µm and was significantly associated with better vision (ß = - 0.083 per 10 µm; R2 = 0.612; P < 0.001). CME was diagnosed in 47.2% (n = 17) eyes. There was no significant difference in mean BCVA for those with CME (0.19 ± 0.2 LogMAR) and without CME (0.40 ± 0.5; R2 = 0.081; P = 0.17). All patients had abnormal UW-FAF. Four main patterns of change were identified (granular 55%, annular 11%, bone spicule 17% and patchy 17%). Patients with the patchy pattern demonstrated worse BCVA in comparison with those with granular (P < 0.0001) and bone spicule (P = 0.0179) patterns. CONCLUSIONS: Structural changes identified on OCT and UW-FAF correlated with BCVA and pERG in this cohort representing different stages of the disease. These parameters could represent reliable biomarkers in therapeutic clinical trials on USH.

Retinal nerve fibre changes in sports-related repetitive traumatic brain injury.

IMPORTANCE: There is limited literature on the use of optical coherence tomography in the assessment of retinal nerve fibre layer (RNFL) thickness in sports-related repetitive mild traumatic brain injury. BACKGROUND: To evaluate RNFL thickness in professional rugby league players. RNFL thinning may serve as a proxy for wider white matter degeneration. DESIGN: Cross-sectional observational study. PARTICIPANTS: Thirteen retired Australian professional rugby league players were recruited. METHODS: Participants underwent binocular optical coherence tomography to measure RNFL thickness. Each participant underwent a complete ophthalmic assessment to exclude concurrent disease. MAIN OUTCOME MEASURES: RNFL thickness of each eye were compared with a normative database. RESULTS: Participants had played professional Rugby League for 18 years on average and reported sustaining 15 sports-related concussions throughout their career. The RNFL in participants was four micrometres thinner than that of matched normative data. Cohort average RNFL thickness was reduced in 12 out of 14 optical coherence testing parameters. These findings were statistically significant in the left inferonasal [P = .013] and left nasal [P = .006] sectors. There was no statistically significant relationship between RNFL thickness and other visual measures. CONCLUSIONS AND RELEVANCE: This study is the first to demonstrate RNFL thinning in a cohort of retired Australian professional Rugby League players. RNFL changes have been shown to correlate with cerebral white matter loss and neurodegeneration. Optical coherence tomography may serve as a safe and economical means of screening for repetitive traumatic brain injury related neurodegeneration in contact sport athletes.

MERTK retinopathy: biomarkers assessing vision loss.

PURPOSE: Mer tyrosine kinase-retinitis pigmentosa (MERTK-RP) causes a primary defect in the retinal pigment epithelium, which subsequently affects rod and cone photoreceptors. The study aims to identify the most appropriate MERTK-RP biomarkers to measure disease progression for deciding the optimum therapeutic trial intervention time. MATERIALS AND METHODS: Patients' data from baseline (BL) and last follow-up (LFU) were reviewed. Best corrected visual acuity (BCVA), spectral domain-optical coherence tomography (SD-OCT), ultra-widefield fundus autofluorescence (UWF-FAF) patterns, kinetic perimetry (KP), and electroretinography (ERG) parameters were analyzed. RESULTS: Five patients were included with the mean age of 17.7 ± 14.4 years old (6.7-42.3) at BL and mean BCVA follow-up of 8.4 ± 5.1 years. Mean BCVA at BL and LFU were 0.84 ± 0.86 LogMAR and 1.14 ± 0.86 LogMAR, respectively. The BCVA decline rate was 0.05 ± 0.03 LogMAR units/year. Ellipzoid zones (EZ) were measurable in eight eyes with mean BL length of 1293.75 ± 421.07 µm and reduction of 140.95 ± 69.28 µm/year and mean BL CMT of 174.2 ± 37.52 µm with the rate of 11.2 ± 12.77 µm declining/year. Full-field ERG (ffERG) and pattern ERG (pERG) were barely recordable. UWF-FAF showed central macular hyper-autofluorescence (hyperAF). KP (III4e and V4e) was normal in two eyes, restricted nasally in four eyes, superior wedge defect in two eyes and undetectable in two eyes. The four restricted nasally KPs became worse, while the others stayed almost unchanged. CONCLUSIONS: This cohort showed early visual loss, moderately rapid EZ reduction and macular hyperAF. EZ, CMT, and BCVA were consistently reduced. Relative rapid decline in these biomarkers reflecting visual function suggests an early and narrow timespan for intervention.