Dark Adaptation Research Articles

An unexpected retained metallic intraocular foreign body.

This case report aims to describe a rare case of asymptomatic retained metallic intraocular foreign body (IOFB) in the retina with reduced full-field electroretinography (ff-ERG) in a Chinese woman. This is a clinical investigation of a patient who unexpectedly presented with a metallic IOFB at the superior-temporal region of the left eye ring during a brain computed tomography. Her best-corrected visual acuity was 20/20 in both eyes. The dilated fundus photograph of the left eye revealed a metallic IOFB in the retina. She reported no ocular symptoms. A diagnosis of asymptomatic metallic IOFB was made definitely. The subsequent ff-ERG demonstrated subnormal amplitudes of dark and light adaption in the left eye, whereas responses were normal in the right eye. Our findings suggest the application of ff-ERG has important benefits for evaluating the visual function in patients with retained IOFB.

Successful Adjunctive Treatment of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) with High-Dose Intravenous Immunoglobulin Therapy (IVIG).

Purpose: The management of bilateral diffuse uveal melanocytic proliferation is controversial, with most earlier reports advocating for plasmapheresis. Here, we report a case of bilateral diffuse uveal melanocytic proliferation secondary to gastric adenocarcinoma that was successfully treated with adjunctive intravenous immunoglobulin, using a loading dose followed by a treat-and-extend strategy. Methods: Clinical case report with 3 years of follow-up including serial ophthalmologic examinations. Functional assessments included visual acuity and subjective visual complaints. Periodic anatomic assessments were performed including serial optical coherence tomography, ultra-widefield fundus imaging, multimodal angiography, and ophthalmic ultrasound. Results: A 75-year-old man presented with a 6-month history of blurry vision and difficulty with dark and light adaptation in both eyes. A diagnosis of bilateral diffuse uveal melanocytic proliferation was established based on clinical findings and subsequent discovery of an underlying gastric malignancy; the diagnosis of a paraneoplastic syndrome was further substantiated by documentation of cancer-associated antiretinal antibodies and serum reactivity against human retina by immunohistochemistry. Treatment with high-dose (2 g/kg) intravenous immunoglobulin was initiated with biweekly, followed by monthly, then q2-3 monthly dosing intervals. Meanwhile, the patient received surgical resection and systemic chemotherapy resulting in complete radiographic remission of the primary cancer. Over the course of 3 years, the patient has demonstrated clinically significant improvements in visual acuity and subjective visual function. Rapid and sustained anatomic improvements were observed in serous retinopathy and choroidal thickness. Conclusion: Intravenous immunoglobulin may be a viable adjunctive treatment option for some patients with bilateral diffuse uveal melanocytic proliferation.

Emergence of metabolic coupling to the heterotroph Alteromonas promotes dark survival in Prochlorococcus

Abstract Prochlorococcus is found throughout the euphotic zone in the oligotrophic open ocean. Deep mixing and sinking while attached to particles can, however, transport Prochlorococcus cells below this sunlit zone, depriving them of light for extended periods of time. Previous work has shown that Prochlorococcus by itself cannot survive extended periods of darkness. However, when co-cultured with a heterotrophic microbe and subjected to repeated periods of extended darkness, Prochlorococcus cells develop an epigenetically inherited dark-tolerant phenotype that can survive longer periods of darkness. Here we examine the metabolic and physiological changes underlying this adaptation using co-cultures of dark-tolerant and parental strains of Prochlorococcus, each grown with the heterotroph Alteromonas under diel light:dark conditions. The relative abundance of Alteromonas was higher in dark-tolerant than parental co-cultures, while dark-tolerant Prochlorococcus cells were larger, contained less chlorophyll, and were less synchronized to the light:dark cycle. Meta-transcriptome analysis revealed that dark-tolerant co-cultures undergo a joint change, in which Prochlorococcus undergoes a relative shift from photosynthesis to respiration, while Alteromonas shifts towards using more organic acids instead of sugars. Furthermore, the transcriptome data suggested enhanced biosynthesis of amino acids and purines in dark-tolerant Prochlorococcus and enhanced degradation of these compounds in Alteromonas. Collectively, our results demonstrate that dark adaptation involves a strengthening of the metabolic coupling between Prochlorococcus and Alteromonas, presumably mediated by an enhanced, and compositionally modified, carbon exchange between the two species.

Light-adapted flicker-optoretinography based on raster-scan optical coherence tomography towards clinical translation.

Optoretinography (ORG) is a promising non-invasive and objective technique for assessing retinal function by measuring its response to light stimulation. Optical coherence tomography (OCT) has emerged as a promising tool for implementing ORG due to its three-dimensional imaging capabilities, high sensitivity to nanometer-scale changes induced by light stimulation, and clinical availability. Although ORG has proven feasible in laboratory settings, research-grade OCT systems lack satisfactory usability and cost-effectiveness to be clinically viable. Standard clinical raster-scan OCT systems, with their limited imaging speed, fall short of the requirements for measuring rapid ORG responses. To bridge this gap, we introduce a flicker-ORG modality based on a raster-scan OCT system that resembles standard clinical OCT. This system overcomes speed limitations through an innovative two-stage scanning protocol coupled with a 600 kHz swept source, enabling repeated volume imaging and precise retinal activity measurements over a finite area. Additionally, the light-adapted ORG strategy eliminates the need for dark adaptation, allowing examinations under photopic conditions and thus improving patient compliance. We tested this new ORG method by measuring flicker-induced photoreceptor responses in five healthy subjects. The results demonstrated high repeatability and revealed dependencies of the ORG response on flicker frequency and retinal eccentricity. These findings, combined with the system's utility, cost-effectiveness, and ease of integration into existing technologies, underscore its substantial potential for clinical application.

The Ratio of A400/A1800 Mapping Identifies Chromosomal Regions Containing Known Photoprotection Recovery-Related Genes in Rice

The rice, like other plants, undergoes photoprotection mode by increasing nonphotochemical quenching (NPQ) in high light intensity (> 1200 µmol m− 2s− 1 PPFD), which attenuates photosystem II yield (φPSII) drastically. The plant remains in photoprotection mode even after light intensity becomes not stressful for an extended period. While there are significant differences in the time it takes for photoprotection to recover among different genotypes, its use is limited in plant breeding because measuring the chlorophyll fluorescence parameters in progressive actinic light after dark adaptation takes more than forty-five minutes per genotype. The study finds that instantly measured A400/A1800 ratio by five minutes in flag leaves of 25 diverse genotypes strongly associated with the φPSII400 differences between theoretical and actual, qPd400 and NPQ400 with R2 values 0.74, 0.65 and 0.60, respectively. In two consecutive years, GWAS of A400/A1800 ratio identified the regions with genes reported earlier for plant photoprotection recovery. Additionally, QTL analysis in a RIL population also identified the regions carrying known genes related to photoprotection. Thus, the A400/A1800 ratio can quickly phenotype many plants for easier introgression of the traits in popular cultivars. The identified genotypes, genes, and QTLs can be used to improve yield potential and allele mining.

Interim safety and efficacy of gene therapy for RLBP1-associated retinal dystrophy: a phase 1/2 trial

Gene therapy holds promise for treatment of inherited retinal dystrophies, a group of rare genetic disorders characterized by severe loss of vision. Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene therapy clinical trial in 12 patients with retinal dystrophy caused by biallelic mutations in the retinaldehyde-binding protein 1 (RLBP1) gene of the visual cycle. The primary endpoints were systemic and ocular safety and recovery of dark adaptation. Secondary endpoints included microperimetry, visual field sensitivity, dominant eye test and patient-reported outcomes. Subretinal delivery of an adeno-associated viral vector (AAV8-RLBP1) was well tolerated with dose-dependent intraocular inflammation which responded to corticosteroid treatment, and focal atrophy of the retinal pigment epithelium as the dose limiting toxicity. Dark adaptation kinetics, the primary efficacy endpoint, improved significantly in all dose-cohorts. Treatment with AAV8-RLBP1 resulted in the resolution of disease-related retinal deposits, suggestive of successful restoration of the visual cycle. In conclusion, to date, AAV8-RLBP1 has shown preliminary safety and efficacy in patients with RLBP1-associated retinal dystrophy. Trial number: NCT03374657.

Does Blacklight Illumination Improve Speed and Accuracy of Foot Pedal Activation in the Low-Light Operating Room?

Background: Urologists frequently activate foot pedals in a low-light operating room (OR). Pedal activation in low-light conditions poses the potential for incorrect pedal activation, potentially leading to increased radiation exposure, patient burns, or OR fires. This study compares speed, accuracy, dark adaptation, and surgeon preference for pedal activation in 4 lighting conditions. Materials and Methods: During a simulated percutaneous nephrolithotomy (PCNL), pedals for C-arm, laser, and ultrasonic lithotripter (USL) were randomized to 3 different positions. Urology attendings, residents, and medical students activated pedals in a randomized order in 4 settings: a dark OR with no illumination, an OR with overhead illumination, a dark OR with glowstick illumination, and a dark OR with blacklight illumination. Endpoints included pedal activation time; number of attempted, incomplete, and incorrect activations; dark adaptation; and subjective pedal preference. ANOVA was used for analysis with p < 0.05 considered significant. Results: In our study with 20 participants, the mean pedal activation times were significantly faster when using glowstick illumination (6.77 seconds) and blacklight illumination (5.34 seconds) compared with the no illumination arm (8.47 seconds, p < 0.001). Additionally, individual pedal activations for the C-arm, laser, and USL were significantly faster with glowstick and blacklight illumination compared with a dark OR (p < 0.001 for all). The blacklight illumination arm demonstrated decreased attempted (0.30 vs. 3.45, p < 0.001), incomplete (1.25 vs. 7.75, p < 0.001), and incorrect activations (0.35 vs. 1.25, p < 0.001) compared with the dark setting, while demonstrating no difference compared with having room lights on. Dark adaptation was significantly improved with blacklight illumination compared with having the room lights on (134.5 vs. 140.5 luminance, p < 0.001). All participants (100%) preferred illuminated pedals compared with the dark OR, with 90% favoring the blacklight illumination. Conclusions: During a simulated PCNL, blacklight illumination significantly improved accuracy and efficiency of pedal activation compared with the conventional dark OR, while maintaining the surgeon's dark adaptation.

Extent and Topography of Subretinal Drusenoid Deposits Associate With Rod-Mediated Vision in Aging and AMD: ALSTAR2 Baseline.

In AMD, rod-mediated dark adaptation (RMDA) at 5° eccentricity is slower in eyes with subretinal drusenoid deposits (SDDs) than in eyes without. Here we quantified SDD burden using supervised deep learning for comparison to vision and photoreceptor topography. In persons ≥60 years from the Alabama Study on Early Age-Related Macular Degeneration 2, normal, early AMD, and intermediate AMD eyes were classified by the AREDS nine-step system. A convolutional neural network was trained on 55°-wide near-infrared reflectance images for SDD segmentation. Trained graders annotated ground truth (SDD yes/no). Predicted and true datasets agreed (Dice coefficient, 0.92). Inference was manually proofread using optical coherence tomography. The mean SDD area (mm2) was compared among diagnostic groups (linear regression) and to vision (age-adjusted Spearman correlations). Fundus autofluorescence images were used to mask large vessels in SDD maps. In 428 eyes of 428 persons (normal, 218; early AMD, 120; intermediate AMD, 90), the mean SDD area differed by AMD severity (P < 0.0001): 0.16 ± 0.87 (normal), 2.48 ± 11.23 (early AMD), 11.97 ± 13.33 (intermediate AMD). Greater SDD area was associated with worse RMDA (r = 0.27; P < 0.0001), mesopic (r = -0.13; P = 0.02) and scotopic sensitivity (r = -0.17; P < 0.001). SDD topography peaked at 5° superior, extended beyond the Early Treatment of Diabetic Retinopathy Study grid and optic nerve, then decreased. SDD area is associated with degraded rod-mediated vision. RMDA 5° (superior retina) probes where SDD is maximal, closer to the foveal center than the rod peak at 3 to 6 mm (10.4°-20.8°) superior and the further eccentric peak of rod:cone ratio. Topographic data imply that factors in addition to rod density influence SDD formation.

Oscillatory potential findings in patients with acute ischaemic central retinal vein occlusion

AimsTo explore the sensitive components of full-field electroretinography (ERG) as indicators of retina function at the onset of acute ischaemic central retinal vein occlusion (CRVO).Methods11 patients (11 eyes) with ischaemic...

Pupillary Light Reflex Reveals Melanopsin System Alteration in the Background of Myopia-26, the Female Limited Form of Early-Onset High Myopia.

The purpose of this study was to evaluate pupillary light reflex (PLR) to chromatic flashes in patients with early-onset high-myopia (eoHM) without (myopic controls = M-CTRL) and with (female-limited myopia-26 = MYP-26) genetic mutations in the ARR3 gene encoding the cone arrestin. Participants were 26 female subjects divided into 3 groups: emmetropic controls (E-CTRL, N = 12, mean age = 28.6 ± 7.8years) and 2 myopic (M-CTRL, N = 7, mean age = 25.7 ± 11.5years and MYP-26, N = 7, mean age = 28.3 ± 15.4years) groups. In addition, one hemizygous carrier and one control male subject were examined. Direct PLRs were recorded after 10-minute dark adaptation. Stimuli were 1-second red (peak wavelength = 621nm) and blue (peak wavelength = 470nm) flashes at photopic luminance of 250 cd/m². A 2-minute interval between the flashes was introduced. Baseline pupil diameter (BPD), peak pupil constriction (PPC), and postillumination pupillary response (PIPR) were extracted from the PLR. Group comparisons were performed with ANOVAs. Dark-adapted BPD was comparable among the groups, whereas PPC to the red light was slightly reduced in patients with myopia (P = 0.02). PIPR at 6 seconds elicited by the blue flash was significantly weaker (P < 0.01) in female patients with MYP-26, whereas it was normal in the M-CTRL group and the asymptomatic male carrier. L/M-cone abnormalities due to ARR3 gene mutation is currently claimed to underlie the pathological eye growth in MYP-26. Our results suggest that malfunction of the melanopsin system of intrinsically photosensitive retinal ganglion cells (ipRGCs) is specific to patients with symptomatic MYP-26, and may therefore play an additional role in the pathological eye growth of MYP-26.

Shine Amidst Darkness—A Case of Oguchi Disease

Abstract An 11-year-old boy presented with complaints of defective night vision. Visual acuity was 6/6 in both eyes. The fundus showed a golden-to-grey discoloration in light and on dark adaptation, the fundus reverted to its normal appearance demonstrating the classical Mizuo-Nakamura phenomenon. The electroretinogram showed abnormal rod responses and normal photopic responses. An electroretinogram done after overnight dark adaptation showed partial recovery with subsequent attenuation. Screening of family members showed abnormal electroretinogram findings in his father and brother. This case is portrayed on account of its rarity.

Choriocapillaris Impairment, Visual Function, and Distance to Fovea in Aging and Age-Related Macular Degeneration: ALSTAR2 Baseline.

In aging and early-intermediate age-related macular degeneration (AMD), rod-mediated dark adaptation (RMDA) slows more at 5° superior than at 12°. Using optical coherence tomography angiography (OCTA), we asked whether choriocapillaris flow deficits are related to distance from the fovea. Persons ≥60years stratified for AMD via the Age-Related Eye Disease Study's nine-step system underwent RMDA testing. Two adjacent 4.4° × 4.4° choriocapillaris OCTA slabs were centered on the fovea and 12° superior. Flow signal deficits (FD%) in concentric arcs (outer radii in mm, 0.5, 1.5, 2.2, 4.0, and 5.0 superior) were correlated with rod intercept time (RIT) and best-corrected visual acuity (BCVA). In 366 eyes (170 normal, 111 early AMD, 85 intermediate AMD), FD% was significantly worse with greater AMD severity in all regions (overall P < 0.05) and poorest under the fovea (P < 0.0001). In pairwise comparisons, FD% worsened with greater AMD severity (P < 0.05) at distances <2.2mm. At greater distances, eyes with intermediate, but not early AMD differed from normal eyes. Foveal FD% was more strongly associated with longer RIT at 5° (r = 0.52) than RIT at 12° (r = 0.39) and BCVA (r = 0.21; all P < 0.0001). Choroidal thickness was weakly associated with longer RIT at 5° and 12° (r = 0.10-0.20, P < 0.05) and not associated with AMD severity. Reduced transport across the choriocapillaris-Bruch's membrane-retinal pigment epithelium complex, which contributes to drusen formation under the macula lutea (and fovea), may also reduce retinoid resupply to rods encircling the high-risk area. FD% has potential as a functionally validated imaging biomarker for AMD emergence.

Relative foveal dark adaptation: a potential method for assessing macular health.

Dark adaptation measures photoreceptor recovery following intense light stimulation. Time to recovery reflects retinal function. We describe a novel method of relative foveal dark adaptation using an iPhone. Data from a small number of healthy subjects were studied to assess reproducibility, effects of age, and consider potential clinical utility. Relative foveal dark adaption was studied in 6 normal subjects across ages from 20 to 81 years and across differing testing conditions. Foveal bleaching is produced by fixating a bright white circle on an iPhone for variable times. After foveal bleaching an annular surround appears to complete a bullseye stimulus with surround initially brighter than centre. As the fovea recovers the centre regains brightness. Relative foveal dark adaptation, the time for the visual anchor to shift from surround to centre, was studied across a range of bleaching times, ages, and testing conditions. Dispersion of dark adaptation times grows with increasing age. Foveal bleaching for 30 s was as effective as longer times. Testing times with a 30 s bleach were less than 1 min. Foveal dark adaptation was reproducible within each subject and was unaffected by ambient room lighting, pupil size, and light attenuation. Repeat, immediately sequential testing was similarly reproducible except after long bleaching. This method of dark adaptation is intuitive, repeatable, and relatively unaffected by testing condition. Testing times are brief, requiring only an iPhone screen positioned at reading distance. Relative foveal dark adaptation may be a useful tool to assess macular health.

Ocular Changes in Cystic Fibrosis: A Review.

Cystic fibrosis (CF), also known as mucoviscidosis, is the most common autosomal recessive genetic disease in the Caucasian population, with an estimated frequency of 1:2000-3000 live births. CF results from the mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene localized in the long arm of chromosome 7. The product of CFTR gene expression is CFTR protein, an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that regulates the transport of chloride ions (Cl-) across the apical cell membrane. Primary manifestations of CF include chronic lung and pancreas function impairment secondary to the production of thick, sticky mucus resulting from dehydrated secretions. It is well known that CF can cause both anterior and posterior ocular abnormalities. Conjunctival and corneal xerosis and dry eye disease symptoms are the most characteristic manifestations in the anterior segment. In contrast, the most typical anatomical and functional changes relating to the posterior segment of the eye include defects in the retinal nerve fiber layer (RNFL), vascular abnormalities, and visual disturbances, such as reduced contrast sensitivity and abnormal dark adaptation. However, the complete background of ophthalmic manifestations in the course of CF has yet to be discovered. This review summarizes the current knowledge regarding ocular changes in cystic fibrosis.

Detailed Insight into the Behaviour of Chlorophyll a Fluorescence Transient Curves and Parameters during Different Times of Dark Adaptation in Sunflower Leaves

The reason for this examination is today’s wide usage of chlorophyll a fluorescence (ChlF) among researchers worldwide to measure photosynthetic efficiency. Although the instructions of the ChlF measuring device clearly emphasize the need for methodology adjustments, depending on the specific plant species, many researchers use the usual 30 min of dark adaptation before measurement. Namely, before any ChlF measurement, it is necessary to determine the specific duration of the leaf adaptation to the conditions of darkness of each plant tissue. Because of the numerous uses of the ChlF measurements, we decided to conduct this research to determine whether the appearance of the curves and parameter values depend on the time of sunflower leaf tissue adaptation to dark conditions. Therefore, this research aimed to examine the optimal adaptation time of sunflower tissue to dark conditions to obtain timely precise measurements and credible appearance of ChlF transient curves as well as accurate parameter values. The research was carried out on the sunflower hybrid Luka with 0, 15, 30, 45, 60, 75 and 90 min of dark adaptation in the vegetative, budding and flowering stages in the field conditions. According to the analyzed transient curves and parameters, it was determined that sunflower leaves should be kept in dark conditions for at least 15 min before the measurement of ChlF, which leads to the complete oxidation of PSII and the electron transport chain prior to a saturating pulse of light.

Dominant role for pigment epithelial CRALBP in supplying visual chromophore to photoreceptors

Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment epithelium (RPE) and Müller glia (MG), but the relative functional importance of these two cellular pools is debated. Here, we report RPE- and MG-specific CRALBP knockout (KO) mice and examine their photoreceptor and visual cycle function. Bulk visual chromophore regeneration in RPE-KO mice is 15-fold slower than in controls, accounting for their delayed rod dark adaptation and protection against retinal phototoxicity, whereas MG-KO mice have normal bulk visual chromophore regeneration and retinal light damage susceptibility. Cone pigment regeneration is significantly impaired in RPE-KO mice but mildly affected in MG-KO mice, disclosing an unexpectedly strong reliance of cone photoreceptors on the RPE-based visual cycle. These data reveal a dominant role for RPE-CRALBP in supporting rod and cone function and highlight the importance of RPE cell targeting for CRALBP gene therapies.

ERG Responses in Albinism, Idiopathic Infantile Nystagmus, and Controls.

Our primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate the effect of within-subject changes in nystagmus eye movements on ffERG responses. Dilated Ganzfeld flash ffERG responses were recorded using DTL electrodes under conditions of dark (standard and dim flash) and light adaptation in 68 participants with albinism, 43 with IIN, and 24 controls. For the primary aim, the effect of group and age on ffERG responses was investigated. For the secondary aim, null region characteristics were determined using eye movements recorded prior to ffERG recordings. ffERG responses were recorded near and away from the null regions of 18 participants also measuring the success rate of recordings. For the primary aim, age-adjusted photopic a- and b-wave amplitudes were consistently smaller in IIN compared with controls (P < 0.0001), with responses in both groups decreasing with age. In contrast, photopic a-wave amplitudes increased with age in albinism (P = 0.0035). For the secondary aim, more intense nystagmus significantly reduced the success rate of measurable responses. Within-subject changes in nystagmus intensity generated small, borderline significant differences in photopic b-wave peak times and a-and b-wave amplitudes under scotopic conditions with standard flash. Age-adjusted photopic ffERG responses are significantly reduced in IIN adding to the growing body of evidence of retinal abnormalities in IIN. Differences between photopic responses in albinism and controls depend on age. Success at obtaining ffERG responses could be improved by recording responses at the null region.

Scotopic and Photopic Conventional Visual Acuity and Hyperacuity - Binocular Summation.

The purpose of this study was to determine and compare binocular summation (BiS) of conventional visual acuity (cVA) versus hyperacuity (hVA) for photopic and scotopic luminance conditions as a potential biomarker to assess the outcome of interventions on binocular function. Sixteen young adults (age range [years] = 21-31; 8 women; cVA logMAR < 0.0) participated in this study. The Freiburg Visual Acuity Test (FrACT) was used for VA testing and retested on another day. Both cVA and hVA were determined for dark grey optotypes on light grey background. Participants underwent 40minutes of dark adaptation prior to scotopic VA testing. Binocular and monocular VA testing was performed. The eye with better VA over the 2 days of testing was selected, the BiS was quantified (binocular VA - better monocular VA) and repeated measures ANOVAs were performed. Binocular VA exceeded monocular VA for all luminance conditions, VA-types, and sessions. We report BiS estimates for photopic and scotopic cVA and hVA, (logMAR BiS ± SEM [decimal BiS]): photopic = -0.01 ± 0.01 [1.03] and -0.06 ± 0.03 [1.15]; and scotopic = -0.05 ± 0.01 [1.12] and -0.11 ± 0.04 [1.28], respectively). Improvement for binocular vision estimates ranged from 0.01 to 0.11 logMAR. A repeated-measures ANOVA (RM ANOVA) did not reveal significant effects of LUMINANCE or VA TYPE on BiS, albeit a trend for strongest BiS for scotopic hVA (15% vs. 28%, photopic versus scotopic, respectively) and weakest for photopic cVA (3% vs. 12%, photopic versus scotopic conditions, respectively). Our results indicate that BiS of VA is relevant to scotopic and photopic hVA and cVA. It appears therefore a plausible candidate biomarker to assess the outcome of retinal therapies restoring rod or cone function on binocular vision. Binocular summation of visual acuity might serve as a clinical biomarker to monitor therapy outcome on binocular rod and cone-mediated vision.

The Impact of Photopigment Bleaching on the Human Rod Photoreceptor Subretinal Space Measured Via Optical Coherence Tomography.

The purpose of this study was to investigate rod photopigment bleaching-driven intrinsic optical signals (IOS) in the human outer retina and its measurement repeatability based on a commercial optical coherence tomography (OCT) platform. The optical path length of the rod photoreceptor subretinal space (SRS), that is, the distance between signal bands of rod outer segment tips and retinal pigment epithelium, was measured in 15 healthy subjects in ambient light and during a long-duration bleaching white-light exposure. On 2 identical study days (day 1 and day 2 [D1 and D2]), light stimulation resulted in a significant decrease in rod SRS by 21.3 ± 7.6% and 19.8 ± 8.5% (both P<0.001), respectively. The test-retest reliability of the SRS maximum change of an individual subject was moderate for single measures (intraclass correlation coefficient [ICC] = 0.730, 95% confidence interval [CI] = 0.376, 0.900, P<0.001) and good for average measures (ICC = 0.844, 95% CI = 0.546, 0.947, P<0.001). The mean area under the stimulus response curve with values of 14.8 ± 9.4 and 15.5 ± 7.5µm × minutes (P=0.782) showed excellent agreement between the stimulus response on D1 and D2. Intermittent dark adaptation of the retina led to an initial increase of the SRS by 6.1% (P=0.018) and thereafter showed a decrease toward baseline, despite continued dark adaptation. The data indicate the potential of commercial OCT in measuring slow IOS in the outer retina suggesting that the rod SRS could serve as a biomarker for photoreceptor function. The presented approach could provide an easily implementable clinical tool for the early detection of diseases affecting photoreceptor health.

Electroretinographic oscillatory potentials in Leber hereditary optic neuropathy.

Leber hereditary optic neuropathy (LHON) affects retinal ganglion cells causing severe vision loss. Pattern electroretinogram and photopic negative response (PhNR) of the light-adapted (LA) full-field electroretinogram (ERG) are typically affected in LHON. In the present study, we evaluated dark-adapted (DA) and LA oscillatory potentials (OPs) of the flash ERG in genetically characterized LHON patients to dissociate slow from fast components of the response. Seven adult patients (mean age = 28.4 ± 5.6) in whom genetic diagnosis confirmed LHON with mtDNA or nuclear DNAJC30 (arLHON) pathogenic variants were compared to 12 healthy volunteers (mean age = 35.0 ± 12.1). Full-field ERGs were recorded from both eyes. Offline digital filters at 50, 75 and 100Hz low cutoff frequencies were applied to isolate high-frequency components from the original ERG signals. ERG a-waves and b-waves were comparable between LHON patients and controls, while PhNR was significantly reduced (p = 0.009) in LHON patients compared to controls, as expected. OPs derived from DA signals (75Hz low cutoff frequency) showed reduced peak amplitude for OP2 (p = 0.019). LA OP differences between LHON and controls became significant (OP2: p = 0.047, OP3: p = 0.039 and OP4: p = 0.013) when the 100Hz low-cutoff frequency filter was applied. Reduced OPs in LHON patients may represent disturbed neuronal interactions in the inner retina with preserved photoreceptoral (a-wave) to bipolar cell (b-wave) activation. Reduced DA OP2 and high-cutoff LA OP alterations may be further explored as functional measures to characterize LHON status and progression.