Replication of Reduced Pattern Electroretinogram Amplitudes in Depression With Improved Recording Parameters

Background: The retina has gained increasing attention in non-ophthalmological research in recent years. The pattern electroretinogram (PERG), a method to evaluate retinal ganglion cell function, has been used to identify objective correlates of the essentially subjective state of depression. A reduction in the PERG contrast gain was demonstrated in patients with depression compared to healthy controls with normalization after remission. PERG responses are not only modulated by stimulus contrast, but also by check size and stimulation frequency. Therefore, the rationale was to evaluate potentially more feasible procedures for PERG recordings in daily diagnostics in psychiatry.Methods: Twenty-four participants (12 patients with major depression (MDD) and 12 age- and sex-matched healthy controls) were examined in this pilot study. We investigated PERG amplitudes for two steady-state pattern reversal frequencies (12.5/18.75 rps) and four sizes of a checkerboard stimulus (0.8°, 1.6°, 3.2°, and 16°) to optimize the PERG recordings in MDD patients.Results: Smaller PERG amplitudes in MDD patients were observed for all parameters, whereby the extent of the reduction appeared to be stimulus-specific. The most pronounced decline in the PERG of MDD patients was observed at the higher stimulation frequency and the finest pattern, whilst responses for the largest check size were less affected. Following the PERG ratio protocol for early glaucoma, where similar stimulus dependent modulations have been reported, we calculated PERG ratios (0.8°/16°) for all participants. At the higher frequency (18.75 rps), significantly reduced ratios were observed in MDD patients.Conclusion: The “normalization” of the PERG responses—via building a ratio—appears to be a very promising approach with regard to the development of an objective biomarker of the depressive state, facilitating inter-individual assessments of PERG recordings in patients with psychiatric disorders.

Impact of femtosecond laser-assisted in situ keratomileusis on retinal ganglion cell function

Purpose: To analyse the effect of femtosecond laser-assisted in situ keratomileusis (FS-LASIK) on the electrical response of retinal ganglion cells using pattern electroretinography (pERG). Methods: This was a longitudinal, prospective, observational pilot study. We included consecutive myopic patients who underwent FS-LASIK to correct up to 6 dioptres of myopia and up to 2 dioptres of astigmatism. Patients with excessive blinking or tearing and those with Snellen uncorrected visual acuity less than 0.9 dec on postop day 1 were excluded. Diopsys NOVA® (Diopsys Inc., NJ) pERG records, using high- and low-contrast patterns, were obtained 16 h and 1 month after FS-LASIK was performed. Magnitude (μV), Magnitude D (μV), Magnitude D/Magnitude ratio and signal-to-noise ratio (dB) were analysed. Wilcoxon test for nonparametric paired data was employed. Results: pERG data from 24 eyes were analysed from 24 patients who underwent FS-LASIK. Mean age was 35.79 ± 9.86 years. Mean preoperative refraction was −2.69 ± 7.6 D (spherical) and −0.38 ± 0.40 D (cylinder). Mean surgical time was 56.88 ± 7.6 s. No statistically significant differences were obtained for any of the studied parameters when comparing 16 h with 1 month after FS-LASIK, with the exception of Magnitude with low contrast, which increased from 1.21 ± 0.2 to 1.39 ± 0.29 µV at 16 h and 1 month postoperatively, respectively ( p = 0.03). Conclusions: FS-LASIK seems to induce a mild and transitory defect in retinal ganglion cell function. Only a mild decrease was detected in the magnitude value for low-contrast stimuli when pERG was performed 16 h postoperatively, and it returned to normal 1 month after surgery.

Citicoline in ophthalmologic practice: neuroprotection in ischemic optic neuropathy, diabetic retinopathy and amblyopia

Decrease and loss of vision are extremely important problems, quite common conditions that lead to disability. The most common causes are ischemic optic neuropathy, diabetic retinopathy, and amblyopia. The pathogenesis of these disea­ses is characterized by neurodegeneration, loss of structure and function of neurons. Citicoline may be considered for neuroprotection as the drug of choice in these clinical situations. Citicoline has antioxidant and anti-inflammatory properties, it reduces lipid peroxidation and the formation of free radicals, has anti-apoptotic and membrane-protective effects. The drug has a neuromodulatory effect and also contributes to the pre­servation of sphingomyelin, which ensures signal transmission in nerve cells. In ischemic optic neuropathy, oral citicoline can reduce nerve fiber loss and improve retinal ganglion cell function and visual tract function. In diabetic retinopathy, citicoline prevents synapse loss and improves macular and retinal ganglion cell function. In amblyopia, citicoline stimulates the function of neurotransmitters and neuromodulators, including an increase in the activity of endogenous dopamine and, at the same time, an improvement in the vascular aspects of neurological function. Axobrex is a convenient oral form of citicoline. With oral administration, the bioavailability of citicoline exceeds 90 %, Axobrex is non-toxic and very well-tolerated. The dosage regimen of Axobrex is simple, which contributes to satisfactory patient adherence to treatment. The use of Axobrex in patients with ischemic optic neuropathy, diabetic retinopathy, and amblyopia has an optimal balance of benefits and safety and is advisable for neuroprotection.

Improvement in Inner Retinal Function in Glaucoma in Response to Nicotinamide (Vitamin B3) Supplementation: A Crossover Randomized Clinical Trial

ImportanceRetinal ganglion cells endure significant metabolic stress with ageing and glaucoma-related stressors. Injured cells require increased energy for repair but maintain capacity to recover function despite periods of functional loss. Nicotinamide, a precursor of redox co-factor and metabolite, NAD+, is low in serum of patients with primary open-angle glaucoma and its supplementation provides robust protection of retinal ganglion cells by targeting mitochondrial health in glaucoma models. However, the potential of nicotinamide to improve retinal ganglion cell function in humans with glaucoma is yet unknown.ObjectiveTo determine whether nicotinamide supplementation taken in conjunction with conventional IOP-lowering therapy leads to early improvement in retinal ganglion cell function in people with glaucoma.DesignCrossover, double-masked, randomized clinical trial conducted between October 2017 to January 2019.SettingStudy participants recruited from two tertiary care centers in Melbourne, Australia.ParticipantsAdults diagnosed and treated for primary glaucoma. Ninety-four participants assessed for study eligibility.InterventionParticipants randomized to first receive oral placebo or nicotinamide and reviewed six-weekly. Accelerated dosing method utilized; participants commenced 6-week course of 1.5 grams/day followed by 6 weeks of 3.0 grams/day. After 12 weeks, participants crossed over to other intervention for 12 weeks without washout. At each visit, visual function measured using full-field flash electroretinography and white-on-white perimetry.Main outcome measuresPrimary endpoint was change in inner retinal function determined a-priori as change in photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio).ResultsFifty-seven participants (65.5±10.0 years, 39% female) enrolled. PhNR Vmax improved beyond 95% coefficient of repeatability (COR) in 23% of participants following 12 weeks of nicotinamide versus 9% on placebo. Conversely, PhNR Vmax deteriorated in 9% on placebo and 7% on nicotinamide. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (p=0.02) on nicotinamide and 5.2% [-4.2%, 14.6%], (p=0.27) on placebo. Vmax ratio improved on average by 12.6% [5.0%, 20.2%], (p=0.002) following nicotinamide and 3.6% [-3.4%, 10.5%], (p=0.30) on placebo. A concomitant trend for improved visual field mean deviation was observed with 27% improving ≥1dB on nicotinamide and fewer deteriorating ≥1dB (4%) compared to placebo (p=0.02). Moderate correlation was observed between PhNR and visual field change with treatment. Participants demonstrated excellent treatment adherence rates (>94%) and nicotinamide was well tolerated with minimal side effects.Conclusions and RelevanceNicotinamide supplementation can improve inner retinal function in patients receiving concurrent IOP-lowering glaucoma therapy. Further studies are underway to elucidate the effects of long-term nicotinamide supplementation on glaucoma progression.Trial RegistrationANZCTR trial ID: ACTRN12617000809336 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373001