Inner Segment/outer Segment Research Articles

Polarization-resolved analysis of outer retinal bands: investigating ballistic and multiply scattered photons using full-field swept-source optical coherence tomography.

Precise interpretation of the anatomical origins of outer retinal optical coherence tomography (OCT) presents technical challenges owing to the delicate nature of the retina. To address this challenge, our study introduces a novel polarization-sensitive full-field swept-source OCT (FF-SS-OCT) that provides parallel-polarization and cross-polarization OCT measurements, predominantly capturing ballistically reflected photons and multiply scattered photons, respectively. Notably, parallel-polarization OCT unveils layer-like structures more effectively, including the inner plexiform layer (IPL) sub-layers, outer plexiform layer (OPL) sub-layers (in rod-dominant regions), and rod/cone outer segment (OS) tips, compared to cross-polarization OCT, where such sub-layers are not visible. Through a comparative analysis of parallel-polarization and cross-polarization OCT images of the outer retina, we discovered that the 2nd outer retinal OCT band results from contributions from both the ellipsoid zone (EZ) and the inner segment/outer segment (IS/OS) junction. Similarly, the 3rd outer retinal OCT band appears to reflect contributions from both the interdigitation zone (IZ) and photoreceptor OS tips. This polarization-sensitive approach advances our understanding of the origins of outer retinal OCT signals and proposes potential new biomarkers for assessing retinal health and diseases.

Effectiveness of Suprachoroidal Injection of Triamcinolone Acetonide in Diabetic Macular Edema Following Pars Plana Vitrectomy Using a Modified Custom Microneedle.

The present study evaluated the efficacy of suprachoroidal injection of Triamcinolone Acetonide (SCTA) in diabetic macular edema (DME) following pars plana vitrectomy (PPV) using a modified microneedle. A prospective interventional study was conducted on 60 eyes of 60 patients with centrally involved diabetic macular edema following pars plana vitrectomy (PPV). SCTA was performed at the baseline and repeated after 3 months in case of persistent subretinal or intraretinal fluid, central macular thickness (CMT) more than 300 µm or visual loss by more than one line of the Snellen chart. The present study detected significant reduction of the CMT from 498.3 ± 94.8 µm at the baseline to 212.3 ± 11.9 µm after 12 months of injection with p < 0.001 and a significant improvement of best corrected visual acuity (BCVA) from 1 (0.9-1.2) at the baseline to 0.5 (0.3-0.7) after 12 months of injection with p < 0.001. The intraocular pressure (IOP) increased significantly after 3 months of injection with p < 0.001 and then gradually declined to its normal level after 6 months. Inner segment/outer segment (IS/OS) disruption was the only significant predictor of the final CMT; however, the number of injections, IS/OS disruption, baseline BCVA and the HbA1C level were the significant predictors of the final BCVA after injection. Suprachoroidal injection of TA using this microneedle resulted in significant anatomical and functional improvement in previously vitrectomized diabetic macular edema patients with no recorded ocular or systemic adverse events.

Correlation between multifocal electroretinogram and optical coherence tomography findings with visual acuity after vitrectomy surgery for retinal detachment: an observational study

BackgroundDespite the marked increase in the anatomical success rates of macula-off rhegmatogenous retinal detachment (RRD) surgery, patients may still complain about unsatisfactory visual outcome. This study aims to correlate the postoperative corrected distance visual acuity (CDVA) with the mf-ERG (multifocal electroretinogram) and OCT (optical coherence tomography) findings following vitrectomy surgery for RRD.Patients and methodsThis retrospective observational study included 40 eyes of 40 patients who underwent successful vitrectomy surgery for macula-off RRD. CDVA, mf-ERG amplitudes, mf-ERG latencies, the central macular thickness (CMT) and the integrity of the inner segment/outer segment (IS/OS) junction assessed by OCT, were evaluated 6 months postoperatively. The correlations between CDVA with mf-ERG amplitudes, mf-ERG latencies, central macular thickness, and IS/OS junction integrity were analyzed.ResultsThere was a statistically significant moderate positive correlation between CDVA of the studied eyes with mf-ERG amplitudes of N1, P1 and N2 in ring 1 (P = 0.008; P < 0.001 and P = 0.004, respectively), CMT (P < 0.001), and the integrity of IS/OS junction (P < 0.001). There was no significant correlation between CDVA and mf-ERG latencies in ring 1 (P > 0.05). Linear regression analysis revealed that CDVA was significantly associated with mf-ERG amplitudes and the IS/OS junction integrity. In addition, there was a strong positive correlation between mf-ERG amplitudes in ring 1 and the IS/OS junction integrity.ConclusionsThe integrated interpretation of postoperative CDVA, multifocal ERG parameters, and OCT findings provides useful information about functional visual recovery and retinal microstructural changes following vitrectomy for macula-off RRD surgery. The positive correlation between the IS/OS junction integrity and the mf-ERG amplitudes was stronger than the correlation between the IS/OS junction integrity and CDVA suggesting that mf-ERG may be superior to CDVA in reflecting the extent of microstructural damage in the photoreceptor layer.Trial RegistrationClinicaltrials.gov, NCT05993208. Registered 15 August 2023 - Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT05993208.

Biochemical and microstructural determinants of the development of serous retinal detachment secondary to retinal vein occlusion

PurposeTo study the alteration of cytokine factors in aqueous humor and retinal microstructure in the formation of serous retinal detachment (SRD) secondary to retinal vein occlusion. MethodsThe subjects were 39 patients with RVO, of whom 31 patients had SRD (RVO-SRD). Spectral Domain Optical Coherence Tomography (SD-OCT) was used to measure the completeness of photoreceptor inner segment/outer segment (IS/OS) and the external limiting membrane (ELM) as well as the structure of RVO-SRD, including the height and shape of SRD. The aqueous humor was collected before intravitreal injection of Ranibizumab. The concentrations of VEGF, MCP-1, IL-8, IL-6, b-FGF and TNF-α in the aqueous humor were measured. All patients participated in the 6-month follow-up examinations, which included visual acuity, intraocular pressure, ophthalmologic examination, and SD-OCT. The time of recurrence of RVO-SRD was recorded. ResultsThe formation of SRD was associated with the area of congested vein, disrupted IS/OS, ELM layers and high VEGF, MCP-1, IL-8, IL-6 levels. However, the height and shape of SRD were not relevant to any inflammatory factors. Moreover, high levels of MCP-1, IL-8 and IL-6 were found in large areas of congested veins. High levels of MCP-1 and IL-6 were observed in the patients with incomplete IS/OS and ELM. The recurrence of SRD was related to the high MCP-1 level. ConclusionHigh concentrations of cytokine factors in aqueous humor could induce vascular leakage, exacerbate the extent of macular edema, disrupt the structure of ELM and IS/OS, and develop SRD in RVO.

A real-world study for timely assessing the diabetic macular edema refractory to intravitreal anti-VEGF treatment.

Early Identifying and characterizing patients with diabetic macular edema (DME) is essential for individualized treatment and outcome optimization. This study aimed to timely investigate optical coherence tomography (OCT) biomarkers of DME refractory to intravitreal anti-vascular endothelial growth factor (VEGF) therapy. We retrospective reviewed 72 eyes from 44 treatment-naïve patients who were treated with intravitreal anti-VEGF for DME. OCT scans prior to anti-VEGF were evaluated for serous retinal detachment (SRD), size of outer nuclear layer cystoid changes, diffuse retinal thickening, integrity of the inner segment-outer segment (IS-OS) junction, quantity and location of hyperreflective foci, vitreomacular interface abnormalities, and epiretinal membrane (ERM). The Baseline best-corrected visual acuity (BCVA) and central macular thickness was recorded at baseline and 4 months after treatment with anti-VEGF. The main outcome measure was the correlation between spectral-domain OCT measurements and BCVA response at baseline and after anti-VEGF treatment (mean change from baseline; ≥ 10 Early Treatment Diabetic Retinopathy Study letters in BCVA). Partially continuous IS-OS layers (partially vs. completely continuous: β, -0.138; Wald chi-square, 16.392; P<0.001) was predictor of better response to anti-VEGF treatment. In contrast, ERM (present vs. absent ERM: β, 0.215; Wald chi-square, 5.921; P=0.015) and vitreomacular traction (vitreomacular traction vs. posterior vitreous detachment: β=0.259; Wald chi-square=5.938; P=0.015) were the predictors of poor response. The improvement of BCVA trended toward the OCT predictive value of central macular thickness reduction; however, this was not significant. Partially continuous IS-OS layers is predictive of better response to anti-VEGF therapy in DME. Meanwhile, ERM is a significant predictor of poor response.

Are Women with COVID-19 and Migraine Prone to AMN Type 2?

Purpose: To describe 3 cases of acute macular neuroretinopathy (AMN) type 2 associated with SARS-CoV-2 viral infection and migraine. Methods: Observational case series and literature review. Results: The three patients, which were all women in their reproductive years with a mean age of 31 (range, 22-43), were diagnosed with AMN type 2 after presenting with acute onset of uni- or bilateral persisting paracentral scotomata. On multi-modal imaging with near-infrared (NIR) reflectance imaging, wedge-shaped dark-gray lesions were discernable in a perifoveal petaloid configuration. SD-OCT through the lesions revealed initial hyperreflectivity at the level of the outer retina, beneath the OPL (outer plexiform layer) and comprising the ONL (outer nuclear layer), with disruption of the inner segment/outer segment (IS/OS) band, eventually evolving into thinning of the ONL with or without persisting disruption of the photoreceptor complex. Anterior segment, fundoscopic, angiographic and electrophysiologic examinations were unremarkable. Conclusion: All three cases were diagnosed with a concurrent viral upper respiratory tract infection caused by the SARS-CoV-2 virus. While AMN is considered to be a rare disease, a worldwide surge in the incidence of AMN has recently been reported and the largest case series to date have been described during the latest SARS-CoV-2 viral pandemic. Thus, COVID-19 could be considered a potential risk factor for the development of AMN type 2. Two of our cases were associated with migraine, one of which experienced the onset of AMN symptoms in the immediate setting of a migraine attack and the use of triptans. This association between migraine, triptans and AMN type 2 should be considered in the context of a seemingly persisting visual aura, particularly in the presence of additional risk factors, such as female gender and oral contraceptive use. Summary statement An increased incidence of acute macular neuroretinopathy (AMN) type 2 is observed in the context of SARS-CoV-2 viral infection. The presently described association between AMN, migraine, and triptans should be considered when examining a patient with seemingly persisting visual aura, in particular negative scotomata, in the context of migraine.

Solar retinopathy in India: Clinical presentation and demographic distribution in 253 patients (349 eyes).

To describe the demographics, clinical characteristics, and presentation of solar retinopathy in patients who presented to a multi-tier ophthalmology hospital network in India. This cross-sectional, hospital-based study included 3,082,727 new patients presenting to the hospital between August 2010 and December 2021. Patients with a clinical diagnosis of solar retinopathy in at least one eye were included in the study. All the data was collected using an electronic medical record system. Three hundred and forty-nine eyes of 253 (0.01%) patients were diagnosed with solar retinopathy and included in the study, and 157 patients (62.06%) had a unilateral affliction. Solar retinopathy was noted to be significantly more common in males (73.12%) and adults (98.81%). The most common age group at presentation was during the sixth decade of life with 56 (22.13%) patients. They were more commonly from the rural geography (41.9%). Among the 349 eyes, 275 (78.8%) eyes had mild or no visual impairment (<20/70), which was followed by moderate visual impairment (>20/70-20/200) found in 45 (12.89%) eyes. The most commonly associated ocular comorbidity was cataract in 48 (13.75%) eyes, followed by epiretinal membrane in 38 (10.89%) eyes. The most common retinal damage seen was interdigitation zone (IZ) disruption (38.68%), followed by inner segment-outer segment (IS-OS) disruption (33.52%). Foveal atrophy was seen in 105 (30.09%) eyes. Solar retinopathy is predominantly unilateral and is more common in males. It usually presents during the sixth decade of life and rarely causes significant visual impairment. The most common retinal damage seen was disruption of the outer retinal layers.

Derivation of human retinal cell densities using high-density, spatially localized optical coherence tomography data from the human retina.

This study sought to identify demographic variations in retinal thickness measurements from optical coherence tomography (OCT), to enable the calculation of cell density parameters across the neural layers of the healthy human macula. From macular OCTs (n=247), ganglion cell (GCL), inner nuclear (INL), and inner segment-outer segment (ISOS) layer measurements were extracted using a customized high-density grid. Variations with age, sex, ethnicity, and refractive error were assessed with multiple linear regression analyses, with age-related distributions further assessed using hierarchical cluster analysis and regression models. Models were tested on a naïve healthy cohort (n=40) with Mann-Whitney tests to determine generalizability. Quantitative cell density data were calculated from histological data from previous human studies. Eccentricity-dependent variations in OCT retinal thickness closely resemble topographic cell density maps from human histological studies. Age was consistently identified as significantly impacting retinal thickness (p=.0006, .0007, and .003 for GCL, INL and ISOS), with gender affecting ISOS only (p<.0001). Regression models demonstrated that age-related changes in the GCL and INL begin in the 30th decade and were linear for the ISOS. Model testing revealed significant differences in INL and ISOS thickness (p=.0008 and .0001; however, differences fell within the OCT's axial resolution. Qualitative comparisons show close alignment between OCT and histological cell densities when using unique, high-resolution OCT data, and correction for demographics-related variability. Overall, this study describes a process to calculate in vivo cell density from OCT for all neural layers of the human retina, providing a framework for basic science and clinical investigations.

Qihuang Granule protects the retinal pigment epithelium from oxidative stress via regulation of the alternative complement pathway

BackgroundAge-related macular degeneration (AMD) is a leading cause of vision loss in elderly people, and dry AMD is the most common type of AMD. Oxidative stress and alternative complement pathway activation may play essential roles in the pathogenesis of dry AMD. There are no available drugs for dry AMD. Qihuang Granule (QHG) is an herbal formula for the treatment of dry AMD, and it achieves a good clinical effect in our hospital. However, its potential mechanism is unclear. Our study investigated the effects of QHG on oxidative stress-associated retinal damage to reveal its underlying mechanism.MethodsOxidative stress models were established using H2O2 and NaIO3 in ARPE-19 cells and C57BL/6 mice. Cell apoptosis and viability were assessed using phase contrast microscopy and flow cytometry, respectively. Alterations in the mouse retinal structure were evaluated using Masson staining and transmission electron microscopy (TEM). The expression of complement factor H (CFH), complement component 3a (C3a) and complement component 5a (C5a) in retinal pigment epithelium (RPE) cells and mice was measured using RT‒PCR, Western blot analysis and ELISA.ResultsPretreatment with QHG significantly prevented cell apoptosis and disorder of the RPE and inner segment/outer segment (IS/OS) in H2O2-treated RPE cells and NaIO3-injected mice. QHG alleviated mitochondrial damage in mouse RPE cells, as shown by TEM. QHG also promoted CFH expression and inhibited the expression of C3a and C5a.ConclusionsThe results suggest that QHG protects the retinal pigment epithelium from oxidative stress, likely by regulating the alternative complement pathway.

Swept source optical coherence tomography and optical coherence tomography angiography for diagnosis and follow‐up of type 2 macular telangiectasia

AbstractPurpose: To report the contribution of swept source optical coherence tomography (SS‐OCT) and OCT‐angiography (OCTA) imaging findings in the diagnosis and the follow‐up of type 2 macular telangiectasia (MacTel 2).Methods: A retrospective study of eight eyes (five patients) with various stages of MacTel2. Clinical staging of MacTel 2 was performed based on SS‐OCT and OCTA.Results: The average age was 63 years old. The mean follow up was 33.6 months. A very early non‐proliferative stage was found in three eyes, an early non‐proliferative stage in three eyes and a late proliferative stage in two eyes. The most common findings on SS‐OCT were disruption of the inner segment‐outer segment (IS/OS) layer in all eyes, parafoveal hyporeflective retinal cavities in four eyes and superficial retinal crystals in three eyes. Two eyes showed irregularity of foveal contour and internal limiting membrane draping associated with retinal vascular channels connecting the superficial and deep retinal layers and forming retinal‐choroidal anastomosis. OCTA findings included capillary telangiectatic changes and enlargement of intercapillary spaces predominantly in deep capillary plexus (DCP) in comparison with superficial capillary plexus (SCP) in all eyes. Irregularity of capillary size in the perifoveal region of the DCP and SCP, predominantly temporal to the fovea, was found in five eyes. Circumferential capillary distortions and subretinal neovascularization at the level of the outer retina and choriocapillaris were detectable in two eyes. At the mean period of follow‐up, lesions were stable in two eyes, an extension of IS/OS disruption was noted in four eyes, parafoveal cavities' appearance and/or extension was found in two eyes and neovascular proliferation appeared in one eye.Conclusions: SS‐OCT and OCTA imaging features facilitate the diagnosis, staging and long‐term follow‐ up of MacTel 2. Further prospective studies are need to characterize the progressive and sequential nature of structural changes in this disease.

Commentary: Indistinct retinal outer layers in the walls of idiopathic full thickness macular hole - A potential predictive biomarker for surgical outcomes.

Commentary: Indistinct retinal outer layers in the walls of idiopathic full thickness macular hole - A potential predictive biomarker for surgical outcomes.

Effectiveness of Suprachoroidal Injection of Triamcinolone Acetonide in Resistant Diabetic Macular Edema Using a Modified Microneedle.

The present study evaluated the effectiveness of suprachoroidal injection of triamcinolone acetonide (TA) in resistant diabetic macular edema (DME) using a modified microneedle. This is a prospective nonrandomized interventional study that was conducted on 55 eyes of 39 patients with centrally involving DME resistant to previous antivascular endotheli qal growth factor (VEGF) agents. All patients received suprachoroidal injection of triamcinolone acetonide 4 mg/0.1 mL by a modified specialized microneedle. The mean central macular thickness (CMT) decreased sign ificantly from 478.7±170.2 µm before injection to 230.2±47.4 µm after 12 months with p-value <0.001. Significant improvement of the mean best corrected visual acuity (BCVA) from 1.193±0.2 by logMAR at the baseline to 0.76±0.3 by logMAR was achieved after 12 months with p-value <0.001. The IOP increased significantly at one month after injection and returned to the baseline value at the third month. Eyes with more baseline CMT and worse baseline BCVA achieved worse final BCVA 12 months after injection. Eyes with inner segment/outer segment (IS/OS) disruption and neurosensory detachment (NSD) showed worse final visual outcomes. IS/OS segment disruption, NSD and baseline BCVA were the main independent predictors of the final BCVA. Suprachoroidal injection of TA using this new modified microneedle resulted in marked anatomical and functional results in cases of DME resistant to previous anti-VEGF drugs with no serious ocular or systemic side effects. The study was prospectively registered with clinical trial.gov ID (NCT04690608) in 27-12-2020.

Parameters affecting the anatomical and functional success of macular hole surgery

Aim: To evaluate the effect of preoperative Spectral Domain Optical Coherence Tomography (SD-OCT) parameters on macular hole surgery (MHS) and their predictive value for postoperative best corrected visual acuity (BCVA).&#x0D; Materials and Methods: This retrospective study included 30 eyes of 30 patients with macular hole (MH). All patients underwent pars plana 23-gauge vitrectomy. A detailed macular analysis including MH minimum diameter (MD), base diameter (BD), opening diameter (OD), height, nasal arm (NA), temporal arm (TA), macular hole index (MHI), diameter hole index (DHI), tractional hole index (THI), hole form factor (HHF), macular hole area (MHA), and macular hole volume (MHV) were performed preoperatively. Presence of inner segment–outer segment (IS/OS) line, external limiting membrane (ELM), and cyst was noted postoperatively. Relationships between these parameters and postoperative BCVA were evaluated.&#x0D; Results: The study group comprised 25 (83.3%) women. Mean pre and postoperative BCVA values were 0.924±0.320 and 0.487±0.287 logMAR, respectively. BCVA improved significantly after MHS (p

Subcellular Comparison of Visible-Light Optical Coherence Tomography and Electron Microscopy in the Mouse Outer Retina.

PurposeWe employed in vivo, 1.0-µm axial resolution visible-light optical coherence tomography (OCT) and ex vivo electron microscopy (EM) to investigate three subcellular features in the mouse outer retina: reflectivity oscillations inner to band 1 (study 1); hyperreflective band 2, attributed to the ellipsoid zone or inner segment/outer segment (IS/OS) junction (study 2); and the hyperreflective retinal pigment epithelium (RPE) within band 4 (study 3).MethodsPigmented (C57BL/6J, n = 10) and albino (BALB/cJ, n = 3) mice were imaged in vivo. Enucleated eyes were processed for light and electron microscopy. Using well-accepted reference surfaces, we compared micrometer-scale axial reflectivity of visible-light OCT with subcellular organization, as revealed by 9449 annotated EM organelles and features across four pigmented eyes.ResultsIn study 1, outer nuclear layer reflectivity peaks coincided with valleys in heterochromatin clump density (−0.34 ± 2.27 µm limits of agreement [LoA]). In study 2, band 2 depth on OCT and IS/OS junction depth on EM agreed (−0.57 ± 0.76 µm LoA), with both having similar distributions. In study 3, RPE electron dense organelle distribution did not agree with reflectivity in C57BL/6J mice, with OCT measures of RPE thickness exceeding those of EM (2.09 ± 0.89 µm LoA). Finally, RPE thickness increased with age in pigmented mice (slope = 0.056 µm/mo; P = 6.8 × 10−7).ConclusionsVisible-light OCT bands arise from subcellular organization, enabling new measurements in mice. Quantitative OCT–EM comparisons may be confounded by hydration level, particularly in the OS and RPE. Caution is warranted in generalizing results to other species.

Recovery course of foveal microstructure in the nonsurgical resolution of full-thickness macular hole.

To analyze the recovery course of foveal microstructures in eyes with nonsurgical healing of full-thickness macular hole (FTMH). By serial OCT scans, the temporal healing sequences were analyzed in ocular trauma, vitreomacular traction (VMT), cystoid macular edema (CME), and the remaining group. We evaluated correlations between the final best-corrected spectacle visual acuity and reconstruction time of external limiting membrane (ELM), and inner segment/outer segment (IS/OS). The healing (mean±standard deviation in months) most involved fusion at the level of the outer nuclear layer (ONL) (6.3±10.5) followed by restoration of ELM (9.1±13.8), and lastly, by IS/OS regeneration (13.1±19.5). In severe blunt ocular trauma, healing was fast and involved subretinal zipper glue-like reapposition with resulting outer retinal atrophy. Best spectacle-corrected visual acuity correlated with normalization of the clivus (p=0.012), faster ELM (p=0.006), and IS/OS reconstitution (p=0.024). Recurrence of FTMH occurred when the healing was halted (3 eyes) or was aberrant by lamellar hole epiretinal proliferation (LHEP) (3 eyes) or by the persistence of VMT (1 eye). Recovery sequences proceeded from the ONL to the deeper layers with BCVA correlating absolutely and temporally with the restoration of outer retinal layer integrity.

Correlation Between Fundus Fluorescein Angiography (Ffa), Optical Coherence Tomography (Oct) And Visual Acuity In Eyes With Broken Foveal Avascular Zone (Faz)

Purpose: To identify the correlation between the broken foveal avascular zone (FAZ) on fundus fluorescein angiography (FFA) with the outer retinal changes on the optical coherence tomography (OCT) and its relationship with visual acuity. Methods: The study included the patients with diabetic retinopathy, non-proliferative and proliferative, with broken FAZ on FFA, and were compared with the controls selected from the eyes without retinopathy and intact FAZ. The OCT scanning with enhanced depth imaging (EDI) through the area of broken FAZ was reviewed. Results: Thirty eyes (mean age 51+12.92 years) with broken FAZ were included-18 eyes showed broken inner segment- outer segment (IS-OS) on OCT (p=0.21). Mean diabetic age was 8.3+4.01 years. Eight eyes in the study group had &gt;20/30 best-corrected visual acuity (p=0.26). Macular thickness and visual acuity did not have a linear correlation. The duration of diabetes had a significant correlation with broken IS-OS junction (p=0.004). The odds of poor vision with broken FAZ were 2.5 (95% CI 0.5-12.4). The positive predictive value (PPV) of disrupted IS-OS junction in broken FAZ was 47.37% (95% CI (range 30.98% to 64.18%) and the negative predictive value (NPV) of intact IS-OS junction in broken FAZ was 50% (95% CI range 29.12% to 70.88%). The combined PPV of poor vision (&lt;20/40) and longer diabetic duration (&gt;9 years) was 88.89% (range 51.75% to 99.72%) and the NPV was 100% (range 71.51% to 100%). Conclusion: Disrupted IS-OS junction could indicate an ischemic macula, but correlation with visual acuity is important.

Macular thickness varies with age-related macular degeneration genetic risk variants in the UK Biobank cohort

To evaluate the influence AMD risk genomic variants have on macular thickness in the normal population. UK Biobank participants with no significant ocular history were included using the UK Biobank Resource (project 2112). Spectral-domain optical coherence tomography (SD-OCT) images were taken and segmented to define retinal layers. The influence of AMD risk single-nucleotide polymorphisms (SNP) on retinal layer thickness was analysed. AMD risk associated SNPs were strongly associated with outer-retinal layer thickness. The inner-segment outer segment (ISOS)-retinal pigment epithelium (RPE) thickness measurement, representing photoreceptor outer segments was most significantly associated with the cumulative polygenic risk score, composed of 33 AMD-associated variants, resulting in a decreased thickness (p = 1.37 × 10–67). Gene–gene interactions involving the NPLOC4-TSPAN10 SNP rs6565597 were associated with significant changes in outer retinal thickness. Thickness of outer retinal layers is highly associated with the presence of risk AMD SNPs. Specifically, the ISOS-RPE measurement. Changes to ISOS-RPE thickness are seen in clinically normal individuals with AMD risk SNPs suggesting structural changes occur at the macula prior to the onset of disease symptoms or overt clinical signs.

Conditional Deletion of Cytoplasmic Dynein Heavy Chain in Postnatal Photoreceptors.

PurposeCytoplasmic dynein-1 (henceforth dynein) moves cargo in conjunction with dynactin toward the minus end of microtubules. The dynein heavy chain, DYNC1H1, comprises the backbone of dynein, a retrograde motor. Deletion of Dync1h1 abrogates dynein function. The purpose of this communication is to demonstrate effects of photoreceptor dynein inactivation during late postnatal development and in adult retina.MethodsWe mated Dync1h1F/F mice with iCre75 and Prom1-CreERT2 mice to generate conditional rod and tamoxifen-induced knockout in rods and cones, respectively. We documented retina degeneration with confocal microscopy at postnatal day (P) 10 to P30 for the iCre75 line and 1 to 4 weeks post tamoxifen induction (wPTI) for the Prom1-CreERT2 line. We performed scotopic and photopic electroretinography (ERG) at P16 to P30 in the iCre75 line and at 1-week increments in the Prom1-CreERT2 line. Results were evaluated statistically using Student's t-test, two-factor ANOVA, and Welch's ANOVA.ResultsCre-induced homologous recombination of Dync1h1F/F mice truncated DYNC1H1 after exon 23. rodDync1h1−/− photoreceptors degenerated after P14, reducing outer nuclear layer (ONL) thickness and combined inner segment/outer segment (IS/OS) length significantly by P18. Scotopic ERG a-wave amplitudes decreased by P16 and were extinguished at P30. Cones were stable under rod-knockout conditions until P21 but inactive at P30. In tamDync1h1−/− photoreceptors, the IS/OS began shortening by 3wPTI and were nearly eliminated by 4wPTI. The ONL shrank significantly over this interval, indicating rapid photoreceptor degeneration following the loss of dynein.ConclusionsOur results demonstrate dynein is essential for the secretory pathway, formation of outer segments, and photoreceptor maintenance.

Real-life outcomes of intravitreal ranibizumab, aflibercept, and dexamethasone implant administrations in patients with treatment-naïve diabetic macular edema.

PURPOSE:To investigate optical coherence tomography (OCT) biomarker data on visual recovery in treatment-naïve diabetic macular edema (DME) and follow the results of intravitreal ranibizumab (RNB), aflibercept (AFL), and dexamethasone (DEX) implant administration within the 1st year of the pro re nata treatment regimen.METHODS:One hundred and twenty eyes of 102 patients were enrolled in the study. The patients medical records were analyzed retrospectively. Best-corrected visual acuity (BCVA), central macular thickness (CMT), type of DME, presence of subretinal fluid, number and localization of hyperreflective dots, vitreomacular interface disorders, disorganization of the retinal inner layer (DRIL), inner segment/outer segment (IS/OS) junction-external limiting membrane (ELM) status, intraretinal cyst diameter and localization, and subfoveal choroidal thickness were examined in all patients.RESULTS:A statistically significant increase in BCVA and a decrease in CMT were detected in all treatment groups. When cases were evaluated in terms of BCVA before and after treatment, statistically significant differences were observed in the RNB and AFL groups at 1 and 4 months and in the DEX group during the 1st year. In terms of OCT biomarkers, visual recovery was obtained in cases of intact IS/OS-ELM and non-DRIL patients. In the serous macular detachment group, more visual gain was achieved with the RNB (1 and 4 months) and AFL (1, 4, and 6 months) agents compared to the DEX implant. On the other hand, in the group with cystoid macular edema, more visual gain was achieved with RNB compared to the DEX implant in all months, but more visual gain was achieved only in the 1st month with AFL administration.CONCLUSION:Significant improvement was achieved for both BCVA and CMT in all treatment groups. We expect that OCT-based prognostic factors will become more important in the treatment of DME and will be determining factors in the choice of treatment.

Macular Morphology in Patients With Diabetic Retinopathy Treated by ILM Peeling: A Propensity Score-Matched Analysis.

To analyze the effects of vitrectomy combined with internal limiting membrane (ILM) peeling in patients with diabetic retinopathy (DR) by propensity score-matched analysis. Patients with proliferative DR that underwent pars plana vitrectomy were divided into two groups: without or with additional ILM peeling. Propensity score-matched analyses of variables were carried out. Optical coherence tomography (OCT) was conducted at the 6-month follow-up. The primary outcome measures were epiretinal membrane (ERM), intraretinal cystic changes, recurrent macular edema, and blurring of the inner segment/outer segment (IS/OS) margin. There were 41 patients in Group 1 (non-ILM peeling) and 41 patients in Group 2 (ILM peeling). ERM was observed in 11 of 41 eyes (26.8%) in Group 1, and three of 41 eyes (7%) in Group 2 at the 6-month follow-up (P = .019). Intraretinal cystoid changes were observed in 13 eyes of Group 1 and four eyes of Group 2 (P = .014). The median central macular thickness was 250.00 ± 135.09 μm in Group 1 and 235.00 ± 101.55 μm in Group 2 (P = .738). Macular edema was observed in 24 eyes (58.5%) in Group 1 and 19 eyes (46.3%) in Group 2 (P = 0.269). There was no significant difference in foveal dip angle between the groups (P = .820). The IS/OS margin was disrupted in 48.8% and 56.1% of eyes in Groups 1 and 2, respectively, without significant difference. There was also no significant difference in best-corrected visual acuity (BCVA) between two groups before surgery, and there was no significant difference in BCVA between two groups at 6 months after surgery (P = .13). The authors' results indicate that vitrectomy combined with ILM peeling can minimize ERM formation and eliminate intraretinal cystoid changes, but the functional recovery is limited. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:420-425.].