Plexiform Layer Research Articles

91-month follow-up of solitary punctate chorioretinitis in a Chinese patient

BackgroundSolitary Punctate Chorioretinitis (SPC) is a recently identified form of punctate inner choroidopathy (PIC) characterized by a single lesion in the fovea of the macula. Previous studies with a maximum follow-up of 48 months were insufficient. Our review uncovered a case sustained for 91 months.Case presentationA 28-year-old young woman experienced with sudden visual loss in her right eye. Comprehensive examinations, including assessment of best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, noncontact tonometry, fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), optical coherence tomography angiography (OCTA), perimetry, and microperimetry, were conducted. Over 91 months, the lesion slightly enlarged, remained yellow-white and punctate, and stayed in the central macula of the posterior pole. OCT images depicted subsidence in the inner nuclear layer (INL), the outer plexiform layer (OPL), photoreceptor layer, and disruption of the external limiting membrane (ELM), ellipsoid zone, and retinal pigment epithelium (RPE)/Bruch’s membrane complex. Retinal herniation, focal choroidal excavation (FCE), and abnormal vessels in the choriocapillaris were noted. At the slab of the choriocapillaris, OCTA demonstrated that the lesion resembled a linear vascular structure, distinct from the structure of normal choriocapillaris. This confirmed the lesion as an abnormal vascular formation. FAF revealed a punctate hypo-autofluorescence lesion and abnormal hyper-autofluorescence near the optic disc and macula. FFA demonstrated a punctate hyper-fluorescent lesion inferotemporal to the fovea. The vascular structure remained stable without fluid exudation on OCT images, hence anti-vascular endothelial growth factor (anti-VEGF) treatment was not administered. Visual acuity improved from counting fingers to 0.07 in 52 days, reached 0.6 after 15 months, remained at 0.6 from 56 to 80 months, and returned to 0.8 after 91 months, although accompanied by local scotomas. The lesion pattern slightly enlarged without scarring.ConclusionsThroughout long-term follow-up, we had long suspected the presence of choroidal neovascularization (CNV) and found the FCE in the last visit. Eventually, we concluded that SPC could potentially constitute a distinct subtype of PIC. The patient received no treatment, and vision recovered to 0.8. If CNV is suspected in SPC, anti-VEGF treatment may not be necessary without activity on OCT, but close monitoring is essential.

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.

EVALUATION OF MACULAR GANGLION CELL COMPLEX USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN GLAUCOMA SUSPECT PATIENTS AND TO CORRELATE IT WITH NORMAL POPULATION

PURPOSE:. To evaluate macular ganglion cell complex in glaucoma suspect patients and normal population RESULTS The difference between values of neuroretinal rim thickness,rim area,disc area,average CDR,vertical CDR and cup volume among glaucoma suspect and normal (controls) was found to be statistically significant (p value<0.001). The difference between values of superior,nasal,inferior,temporal and average RNFL thickness among glaucoma suspect and normal (controls) was found to be statistically significant(p value<0.001). The difference between values of superotemporal, superior, superonasal, inferonasal, inferior, inferotemporal, average and minimum GCIPL (Ganglion cell Inner plexiform layer) thickness in µm, as estimated on OCT macula, was found to be statistically significant among glaucoma suspect patients and normal (controls) (p value <0.001). Upon applying Spearman’s rho correlation coefficient test in glaucoma suspect patients for GCIPL thickness and RNFL thickness, statistically significant correlation was found between Inferior RNFL thickness with Inferotemporal GCIPL thickness(p value 0.029) and Temporal RNFL thickness with Inferotemporal GCIPL thickness .(p values 0.006). Upon applying Spearman’s rho correlation coefficient test in normal (controls) for GCIPL thickness and RNFL thickness,statistically significant correlation was found between Superior RNFL thickness with Superior GCIPL thickness(p value 0.038), Superior RNFL thickness with Superonasal GCIPL thickness (p values 0.012 ), and Average RNFL thickness with Average GCIPL thickness (p value 0.033) CONCLUSION: In our study we found there is statistically significant reduction in thickness in all measured quadrants of Macular GCIPL and RNFL in glaucoma suspect patients compared to normal. Also, a statistically significant correlation was found between Inferior RNFL thickness with Inferotemporal GCIPL thickness and Temporal RNFL thickness with Inferotemporal GCIPL thickness in glaucoma suspect patients,suggesting good diagnostic ability of inferotemporal macular GCIPL thickness.

Hyper-reflective foci changes in RRMS under natalizumab therapy.

Microglia (MG) is suggested to play an immunopathological role of in Multiple Sclerosis (MS). Since hyper-reflective foci (HRF) might mark MG activation, in vivo analysis by Optic Coherence Tomography (OCT) in MS patients under disease modifying therapies may help to clarify MS immunopathology as well as drug's mechanism of intrathecal action. To analyze HRF in patients treated with Natalizumab (NTZ), a high efficacy therapy for MS. The effect of NTZ on the retina of 36 Relapsing-Remitting MS patients was investigated in a prospective, single-center study. OCT was performed immediately before the first infusion and then between infusion 3 and 4, infusion 6 and 7, infusion 11 and 13. Peripapillary and macular scans were acquired, evaluating peripapillary RNFL thickness, macular volumes (vertical scans), and HRF count (horizontal scan) in Ganglion Cell Layer (GCL), Inner Plexiform Layer (IPL) and Inner Nuclear Layer (INL). Clinical examination was performed every six months. HRF count significantly increased under NTZ therapy (p<0.001) in both GCL (18.85 ± 6.93 at baseline, 28.24 ± 9.55 after 12 months) and IPL (25.73 ± 7.03 at baseline, 33.21 ± 8.50 after 12 months) but remained stable in INL (33.65 ± 7.76 at baseline, 36.06 ± 6.86 after 12 months, p=0.87), while no relevant modification of pRNFL and macular volumes were observed during the study. EDSS remained stable and no clinical relapse was observed between month 6 and 12. In RRMS NTZ affects HRF count in GCL and IPL, but not in INL, suggesting that NTZ does not impact on some aspects of MS immunopathology.

Effects of Cataract on Optic Nerve Head and Macular Analysis Using Optical Coherence Tomography

Purpose: To assess the impact of cataract on optic nerve head (ONH) parameters (disc area, rim area, average cup/disc ratio, vertical cup/disc ratio, cup volume), peripapillary retinal nerve fiber layer (pRNFL) thickness, and macular ganglion cell-inner plexiform layer (mGC-IPL) thickness in patients with glaucoma and in a control group.Methods: A retrospective analysis was conducted on medical records from January to December 2021 for individuals undergoing cataract surgery. This group included normal, glaucoma suspects, and glaucoma patients, totaling 44 individuals and 63 eyes. Measurements of ONH parameters, pRNFL thickness, and mGC-IPL thickness were taken using spectral-domain optical coherence tomography before and after surgery. We analyzed postoperative changes in these parameters and related factors to preoperative segmentation errors.Results: In glaucoma patients, a significant increase in the average thickness of the pRNFL (p = 0.002) was observed after surgery, while no significant changes were seen in ONH parameters and the average thickness of the mGC-IPL (all p &gt; 0.05). Conversely, the control group showed an increase in some areas of mGC-IPL thickness after surgery (p &lt; 0.05). Multivariate regression analysis indicated that in glaucoma patients, thinner preoperative pRNFL and mGC-IPL thickness were predictors of increased average thickness after surgery (p &lt; 0.001 and p = 0.008, respectively).Conclusions: Cataract significantly impacts the pRNFL and mGC-IPL thickness in glaucoma patients, with less effect on ONH parameters. These findings suggest that ONH parameters can be more reliable for monitoring patients undergoing cataract surgery and assessing glaucoma progression simultaneously.

Retinal sublayer analysis in juvenile systemic lupus erythematosus without lupus retinopathy.

We aimed to analyze the thicknesses of the retinal sublayer and peripapillary retinal nerve fiber layer (pRNFL) in patients with juvenile systemic lupus erythematosus (JSLE) without lupus retinopathy. Thirty-six patients with JSLE (36 eyes) and 30 control subjects (30 eyes) were included retrospectively. Demographic data, disease duration, and clinical manifestations were recorded. Optical coherence tomography was used to examine the macula and optic disc. The thicknesses of the retina, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), and pRNFL were measured. The correlation between the thickness of retina and disease duration, erythrocyte sedimentation rate (ESR) were investigated. The retinal thicknesses of I3 and T3 were thinner in the JSLE group than in the control group (P = 0.019, P = 0.043, respectively). The thicknesses of the I3 and S6 sectors of the GCL decreased significantly (P = 0.013, and P = 0.022, respectively). The thickness of the S6 sector of the IPL was reduced in the JSLE group compared with the control group (P = 0.047). The JSLE group showed significant decrease in the thickness of the central sector of the ONL (P = 0.034). No statistically significant differences in INL, OPL, RPE, and pRNFL thicknesses were found. The retinal thicknesses of I3 (r = -0.386, P = 0.020) and T3 (r = -0.384, P = 0.021) presented negative associations with ESR, but had no significant correlations with disease duration. Retinal thinning was observed in patients with JSLE without lupus retinopathy, and this change was more pronounced in the inner layer. Key Points • Retinal thinning occurs in JSLE patients without lupus retinopathy. • Changes in retinal thicknesses are related to the ESR.

Comparative analysis of changes in retinal layer thickness following femtosecond laser-assisted cataract surgery and conventional cataract surgery

BackgroundTo investigate the influence of femtosecond laser-assisted cataract surgery (FLACS) on macula by examining changes in retinal layers after FLACS and to compare these changes with those after conventional cataract surgery (CCS).MethodsThis study included 113 unrelated Korean patients with age-related cataract who underwent CCS or FLACS in Severance Hospital between September 2019 and July 2021. Optical coherence tomography was performed before and 1 month after surgery. The total retinal layer (TRL) was separated into the inner retinal layer (IRL) and outer retinal layer (ORL); moreover, the IRL was subdivided into the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer (INL), outer plexiform layer, and outer nuclear layer. We performed between-group comparisons of the postoperative thickness in each retinal layer and the postoperative differences in retinal thickness. The average retinal thickness of the four inner macular ring quadrants was used for comparative analysis.ResultsCompared with the CCS group, the FLACS group exhibited a thicker ORL (P = 0.004) and a thinner INL (P = 0.007) after surgery. All retinal layer thickness values showed significant postoperative changes regardless of the type of surgery (P < 0.05). The postoperative increase in TRL and IRL thickness was significantly smaller in the FLACS group than in the CCS group (P = 0.027, P = 0.012).ConclusionsThe 1-month postoperative retinal changes were less pronounced in the FLACS group than in the CCS group.

Rates of Choriocapillaris Microvascular Dropout and Macular Structural Changes in Glaucomatous Optic Neuropathy With and Without Myopia

PurposeTo evaluate the association between rates of juxtapapillary choriocapillaris microvasculature dropout (MvD) change and rates of ganglion cell inner plexiform layer (GCIPL) loss in primary open-angle glaucoma (POAG) and glaucoma suspect eyes with and without myopia. DesignCohort study from clinical trial data Methods238 eyes from 155 POAG and glaucoma suspect patients were stratified into no-myopia (axial length (AL) ≤ 24 mm; n = 78 eyes), mild myopia (24 mm< AL ≤ 26 mm; n = 114 eyes), and high myopia (AL > 26 mm; n = 46 eyes). Eyes with a minimum of 3 visits and 1.5 years of follow-up with both optical coherence tomography angiography (OCT-A) and OCT macula scans were included. Presence, area, and angular circumference of juxtapapillary MvD were evaluated on en face choroidal images and horizontal B-scans obtained from OCT-A imaging. ResultsOver the mean follow-up of 4.4 years, the mean MvD area rates of change (95% CI) were largest in high and mild myopia group (0.04 (0.03, 0.05) mm2/year in both groups), followed by the no-myopia group (0.03 (0.02, 0.04) mm2/year). The mean MvD angular circumference rates of change (95% CI) were highest in mild myopia group (8.7o (6.9o, 10.5o)/year) followed by the high myopia and no-myopia groups (8.1o (5.3o, 10.9o)/year, and 7.4o (5.3o, 9.6o)/year, respectively). While the mean global GCIPL thinning rates between eyes with MvD at baseline compared to eyes without were similar in all myopia groups, the rates of MvD area change were significantly faster in all myopia groups with baseline MvD (all p≤0.004). Significant faster rates of MvD angular circumference change were found in the mild myopia group with baseline MvD (p<0.001) only. In multivariable models, the rates of GCIPL thinning over time were significantly associated with rates of MvD angular circumference change and MvD area change (R2=0.33, p<0.001 and R2=0.32, p=0.006, respectively). ConclusionsRates of GCIPL thinning were associated with rates of MvD area and angular circumference change over time in myopic POAG eyes. Utilizing OCT-A to detect MvD may provide an additional tool for monitoring macular structural changes in glaucomatous eyes with myopia.

Linking physiology and demographics, non-ocular pathology and pharmaceutical drug use to standard OCT measures of the inner retina: The PPP project.

To assess the associations between physiology and demographics, non-ocular pathology and pharmaceutical drug use against peri-papillary retinal nerve fibre layer thickness (pRNFL T) and other optical coherence tomography (OCT) inner retinal measures in normal, healthy eyes. A retrospective, cross-sectional study of 705 consecutive participants with bilateral normal, healthy optic nerves and maculae. PRNFL Ts, vertical cup/disc ratio (CDR), cup volume and macular ganglion cell layer-inner plexiform layer (GCL-IPL) Ts were extracted from Cirrus OCT scans, then regressed against predictor variables of participants' physiology and demographics (eye laterality, refraction, intraocular pressure [IOP], age, sex, race/ethnicity, etc.) and non-ocular pathology and pharmaceutical drug use according to the World Health Organisation classifications. Associations were assessed for statistical significance (p < 0.05) and clinical significance (|β| > 95% limits of agreement for repeated measures). A multitude of non-ocular pathology and pharmaceutical drug use were statistically and clinically significantly associated with deviations in standard OCT inner retinal measures, exceeding the magnitude of other factors such as age, IOP and race/ethnicity. Thinner inner retina and larger optic nerve cup measures were linked to use of systemic corticosteroids, sex hormones/modulators, presence of vasomotor/allergic rhinitis and other diseases and drugs (up to -29.3 [-49.88, -8.72] μm pRNFL T, 0.31 [0.07, 0.54] vertical CDR, 0.29 [0.03, 0.54] mm3 cup volume and -10.18 [-16.62, -3.74] μm macular GCL-IPL T; all p < 0.05). Thicker inner retina and smaller optic nerve cup measures were diffusely associated with use of antineoplastic agents, presence of liver or urinary diseases and other diseases and drugs (up to 67.12 [64.92, 69.31] μm pRNFL T, -0.31 [-0.53, -0.09] vertical CDR, -0.06 [-0.11, 0] mm3 cup volume and 28.84 [14.51, 43.17] μm macular GCL-IPL T; all p < 0.05). There are a multitude of systemic diseases and drugs associated with altered OCT inner retinal measures, with magnitudes far exceeding those of other factors such as age, IOP and race/ethnicity. These systemic factors should at least be considered during OCT assessments to ensure precise interpretation of normal versus pathological inner retinal health.

Systemic Arterial Stiffness and Choroidal Microvascular Insufficiency on the Structural Progression of Normal Tension Glaucoma

PurposeTo identify the role of systemic arterial stiffness and choroidal microvascular insufficiency on structural progression of normal-tension glaucoma (NTG). DesignRetrospective cohort study. MethodsA total of 107 early NTG eyes of 88 patients, who underwent pulse wave velocity (PWV) measurements and optical coherence tomography (OCT) angiography (OCT-A) at baseline, were categorized depending on the presence of peripapillary choroidal microvasculature dropout (MvD) and PWV. Differences in glaucomatous progression were analyzed. Structural progression rates were determined using the trend-based analysis of cirrus OCT. ResultsThirty-two eyes displayed choroidal MvD (62.7 (95% CI 58.4-67.0) years old, 53.6% males), and 70 eyes did not show any MvD (59.9 (95% CI 57.1-62.6) years old, 53.3% males) at baseline. Patients were followed for 48.4 (95% CI 40.0-56.8) months. When they were further divided based on PWV (high PWV≥1400cm/sec), those with choroidal MvD and high PWV showed significantly faster thinning in macular ganglion cell-inner plexiform layer (GCIPL; P=0.023). In comparison to those with low PWV and no MvD, eyes with high PWV and MvD in the peripapillary area were likely to show fast structural progression (≤-1.2 µm/year) in the macular GCIPL by odds of 6.019 (95% CI 1.619-38.531, P=0.025). ConclusionsIn NTG eyes, GCIPL thinning was faster when choroidal MvD and high systemic arterial stiffness were present. The simultaneous presence of regional and systemic vascular insufficiency may be associated with rapid glaucoma structural progression in eyes with low baseline intraocular pressure.

Prediction of the Cause of Glaucoma Disease Identified by Glaucoma Optical Coherence Tomography Test in Relation to Diabetes and Hypertension at a National Hospital in Seoul: A Retrospective Study.

Glaucoma remains the primary cause of long-term blindness. While diabetes mellitus (DM) and hypertension (HTN) are known to influence glaucoma, other factors such as age and sex may be involved. In this retrospective study, we aimed to investigate the associations between age, sex, DM, HTN, and glaucoma risk. We employed optical coherence tomography (OCT) conducted using a 200 × 200-pixel optic cube (Cirrus HD OCT 6000, version 10.0; Carl Zeiss Meditec, Dublin, CA, USA). Effects obscured by low-test signals were disregarded. Data were amassed from 1337 patients. Among them, 218 and 402 patients had DM and HTN, respectively, with 133 (10%) exhibiting both. A sex-based comparison revealed slightly greater retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness in females. Patients without DM and HTN were predominantly in their 50 s and 60 s, whereas DM and HTN were most prevalent in those in their 60 s and 70 s. Both RNFL and GCIPL thicknesses decreased with advancing age in most patients. The study revealed that older individuals were more prone to glaucoma than younger individuals, with a higher incidence among patients with DM and HTN and reduced RNFL and GCIPL thicknesses. Furthermore, early detection before advancing age could furnish valuable preventive insights.

Imaging the optic nerve with optical coherence tomography.

Optical coherence tomography (OCT) is a non-invasive imaging technology, which may be used to generate in vivo quantitative and qualitative measures of retinal structure. In terms of quantitative metrics, peripapillary retinal nerve fiber layer (pRNFL) thickness provides an indirect evaluation of axonal integrity within the optic nerve. Ganglion layer measures derived from macular scans indirectly reflect retinal ganglion cell status. Notably, ganglion layer indices are platform dependent and may include macular ganglion cell inner plexiform layer (mGCIPL), ganglion cell layer (GCL), and ganglion cell complex (GCC) analyses of thickness or volume. Interpreted together, pRNFL thickness and ganglion layer values can be used to diagnose optic neuropathies, monitor disease progression, and gauge response to therapeutic interventions for neuro-ophthalmic conditions. Qualitative assessments of the optic nerve head, using cross-sectional transverse axial, en face, and circular OCT imaging, may help distinguish papilledema from pseudopapilloedema, and identify outer retinal pathology. Innovations in OCT protocols and approaches including enhanced depth imaging (EDI), swept source (SS) techniques, and angiography (OCTA) may offer future insights regarding the potential pathogenesis of different optic neuropathies. Finally, recent developments in artificial intelligence (AI) utilizing OCT images may overcome longstanding challenges, which have plagued non-vision specialists who often struggle to perform reliable ophthalmoscopy. In this review, we aim to discuss the benefits and pitfalls of OCT, consider the practical applications of this technology in the assessment of optic neuropathies, and highlight scientific discoveries in the realm of optic nerve imaging that will ultimately change how neuro-ophthalmologists care for patients.

Synaptic Protein Loss in Extracellular Vesicles Reflects Brain and Retinal Atrophy in People With Multiple Sclerosis.

To assess whether the rate of change in synaptic proteins isolated from neuronally enriched extracellular vesicles (NEVs) is associated with brain and retinal atrophy in people with multiple sclerosis (MS). People with MS were followed with serial blood draws, MRI (MRI), and optical coherence tomography (OCT) scans. NEVs were immunocaptured from plasma, and synaptopodin and synaptophysin proteins were measured using ELISA. Subject-specific rates of change in synaptic proteins, as well as brain and retinal atrophy, were determined and correlated. A total of 50 people with MS were included, 46 of whom had MRI and 45 had OCT serially. The rate of change in NEV synaptopodin was associated with whole brain (rho = 0.31; p = 0.04), cortical gray matter (rho = 0.34; p = 0.03), peripapillary retinal nerve fiber layer (rho = 0.37; p = 0.01), and ganglion cell/inner plexiform layer (rho = 0.41; p = 0.006) atrophy. The rate of change in NEV synaptophysin was also correlated with whole brain (rho = 0.31; p = 0.04) and cortical gray matter (rho = 0.31; p = 0.049) atrophy. NEV-derived synaptic proteins likely reflect neurodegeneration and may provide additional circulating biomarkers for disease progression in MS.

Optical coherence tomography assessment of disease activity in cryopyrin-associated periodic syndrome.

Cryopyrin-associated periodic syndrome is a rare autoinflammatory disease caused by gain-of-function mutations or variants in the NLRP3 gene. Clinically, patients suffer from a broad spectrum of both systemic and neurological symptoms. The aim of this study was to determine whether systemic inflammation demonstrated by serum amyloid A (SAA) elevation is associated with neuroinflammation assessed by optical coherence tomography (OCT). Thirty eyes of 15 patients with NLRP3 low penetrance mutations (PwNLRP3) and 20 eyes of 10 age- and sex-matched healthy controls were examined by spectral-domain OCT as part of routine clinical care. All retinal layers and clinical features were evaluated. At baseline no significant retinal neuroaxonal inflammation or degeneration was observed in all measured retinal layers amongst PwNLRP3 compared with healthy controls. In a pooled analysis of all individual OCT time points a significant difference regarding the macular retinal nerve fibre layer was detected. Increased levels of SAA showed a positive association with averaged combined outer plexiform layer and outer nuclear layer volumes (ρ < 0.0001, r2 = 0.35). In cryopyrin-associated periodic syndrome increased combined outer plexiform layer and outer nuclear layer volumes are mirrored by SAA increase, an acute phase reactant indicating systemic inflammation. Our findings identify OCT as a candidate biomarker to monitor subclinical neuroinflammation and to assess disease activity in PwNLRP3.

Sequence of Morphological Changes Preceding Atrophy in Intermediate AMD Using Deep Learning.

Investigating the sequence of morphological changes preceding outer plexiform layer (OPL) subsidence, a marker preceding geographic atrophy, in intermediate AMD (iAMD) using high-precision artificial intelligence (AI) quantifications on optical coherence tomography imaging. In this longitudinal observational study, individuals with bilateral iAMD participating in a multicenter clinical trial were screened for OPL subsidence and RPE and outer retinal atrophy. OPL subsidence was segmented on an A-scan basis in optical coherence tomography volumes, obtained 6-monthly with 36months follow-up. AI-based quantification of photoreceptor (PR) and outer nuclear layer (ONL) thickness, drusen height and choroidal hypertransmission (HT) was performed. Changes were compared between topographic areas of OPL subsidence (AS), drusen (AD), and reference (AR). Of 280 eyes of 140 individuals, OPL subsidence occurred in 53 eyes from 43 individuals. Thirty-six eyes developed RPE and outer retinal atrophy subsequently. In the cohort of 53 eyes showing OPL subsidence, PR and ONL thicknesses were significantly decreased in AS compared with AD and AR 12 and 18months before OPL subsidence occurred, respectively (PR: 20µm vs. 23µm and 27µm [P < 0.009]; ONL, 84µm vs. 94µm and 98µm [P < 0.008]). Accelerated thinning of PR (0.6µm/month; P < 0.001) and ONL (0.8µm/month; P < 0.001) was observed in AS compared with AD and AR. Concomitant drusen regression and hypertransmission increase at the occurrence of OPL subsidence underline the atrophic progress in areas affected by OPL subsidence. PR and ONL thinning are early subclinical features associated with subsequent OPL subsidence, an indicator of progression toward geographic atrophy. AI algorithms are able to predict and quantify morphological precursors of iAMD conversion and allow personalized risk stratification.

Assessing Glaucoma Severity and Progression in Individuals with Asymmetric Axial Length: An Intrapatient Comparative Study

PurposeTo investigate whether there is a difference in inter-eye glaucoma severity and progression in patients with asymmetric axial length DesignLong-term observational study ParticipantsPatients over 20 years of age who had been diagnosed with glaucoma at Seoul National University Hospital, Seoul, Korea, between 2010 and 2020. MethodsPatients diagnosed with glaucoma in both eyes with an axial length difference of more than 1.0 mm were included. Each individual’s eyes were classified into “longer eye” and “shorter eye,” and the baseline and follow-up clinical data were analyzed using the paired test. Main Outcome MeasuresDifferences in clinical characteristics in patients with asymmetric axial length ResultsA total of 190 eyes of 95 glaucoma patients with asymmetric axial length were included in the study. The patients’ mean age was 51.2 ± 12.3 years, and the mean follow-up period was 10.1 ± 3.9 years. There was no difference in the baseline intraocular pressure (IOP) or central corneal thickness (CCT) between longer eyes and shorter eyes. Among the baseline disc parameters, ovality index, beta-zone and gamma-zone parapapillary atrophy (PPA) area were larger in the longer eyes. In the baseline OCT data, the retinal nerve fiber layer (RNFL) thickness and ganglion cell-inner plexiform layer (GCIPL) thickness were thinner in the longer eyes. According to a baseline visual field (VF) test, the mean deviation (MD) and visual field index (VFI) values were significantly lower in the longer eyes. Based on an analysis of glaucoma progression, the rate of change of superior GCIPL (longer eyes : -0.65 μm/yr, shorter eyes : -0.40 μm/yr) , MD (longer eyes : -0.40 dB/yr, shorter eyes : -0.21 dB/yr) , and VFI (longer eyes : -0.92 %/yr, shorter eyes : -0.46 %/yr) were larger in the longer eyes. The greater the difference between the mean IOP and beta-zone PPA area between inter-eyes, the greater the difference in the rate of change of RNFL and GCIPL. Additionally, the greater the difference in IOP fluctuation, the greater the difference in the rate of change between MD and VFI. ConclusionsWhen there was an axial length difference of more than 1.0 mm, glaucoma tended to be more severe and to progress faster in the longer eyes. The inter-eye difference in glaucoma progression rate is related to both mean IOP and IOP fluctuation.

Hyperreflective focuses as a biomarker of multiple sclerosis progression

Purpose: to identify the intraretinal hyperreflective foci (HRF), their specific characteristics, localization features and correlations with the duration of the disease, type of course and previous episodes of optic neuritis (ON) in multiple sclerosis (MS) patients using a high-resolution OCT scanning protocol. Materials and methods. The study included 160 patients (318 eyes) divided into 8 groups, i.e. Group 1: 44 eyes (13.84 %) — MS onset without a history of ON; Group 2: 30 eyes (9.43 %) — debut of MS with ON; Group 3: 56 eyes (17.61 %) — relapsing-remitting MS (RRMS) lasting ≤ 10 years without ON; Group 4: 38 eyes (11.95 %) — RRMS lasting ≤ 10 years with ON; Group 5: 49 eyes (15.41 %) — RRMS lasting ˃ 10 years without ON; Group 6: 37 eyes (11.63 %) — RRMS lasting ˃ 10 years with ON; Group 7: 34 eyes (10.69 %) — secondary progressive MS (SPMS) without ON; Group 8: 30 eyes (9.43 %) — SPMS with ON. Results. HRF were identified in all groups, at the levels of both the outer nuclear layer (ONL) and the inner nuclear layer (INL). Their number increased depending on the duration, type of course, and the presence of ON history. The thickness of the inner layers of the retina corresponded to the average normative indicators in the group with the onset of MS without ON. In the SPMS group after ON, a decrease in the total thickness of ganglions retinal cells layer (GCL) and the inner plexiform layer (IPL) was noted, showing minimal values of both avGCL + IPL (65.83 ± 8.27 μm) and avRNFL (76.37 ± 6.94 μm). High inverse correlations were revealed between avGCL + IPL and the amount of GRF at the levels of ONL and INL (-0.82 and -0.85, respectively, p = 0.01). Conclusions. The presence and quantity of HRF can be considered as a prognostic non-invasive biomarker associated with the duration of MS and the history of ON, allowing one to visualize the penetration of microglia activated by immune cells into the unmyelinated part of the central nervous system, helpful in elucidating their role in the pathogenesis and progression of the disease.

Dysregulated energy and protein homeostasis and the loss of GABAergic amacrine cells in aging retina

Aging is a major risk factor for the development or the worsening of retinal degenerative conditions. The intricate network of the neural retina determined that the retinal aging is a complicated process. The aim of this study is to delineate the transcriptomic changes of major retinal neurons during aging in C57BL/6 mice at single-cell level. We analyzed the transcriptional profiles of the photoreceptor, bipolar, amacrine, and Müller glial cells of 1.5–2 and 24–30 months old mice using single-cell RNA sequencing technique. We selectively confirmed the differences in gene expression using immunofluorescence staining and RNA in situ hybridization analysis. We found that each retinal cell type had unique changes upon aging. However, they all showed signs of dysregulated glucose and energy metabolism, and perturbed proteostasis. In particular, old Müller glia exhibited the most profound changes, including the upregulation of cell metabolism, stress-responses, antigen-presentation and immune responses and metal ion homeostasis. The dysregulated gliogenesis and differentiation was confirmed by the presence of Müller glia expressing rod-specific genes in the inner nuclear layer and the outer plexiform layer of the old retina. We further pinpointed the specific loss of GABAergic amacrine cells in old retina. Our study emphasized changes of amacrine and Müller glia during retinal aging, provided resources for further research on the molecular and cellular regulatory mechanisms underlying aging-associated retinal deterioration.

Visual Field Prognosis From Macula and Circumpapillary Spectral Domain Optical Coherence Tomography.

To explore the structural-functional loss relationship from optic-nerve-head- and macula-centred spectral-domain (SD) Optical Coherence Tomography (OCT) images in the full spectrum of glaucoma patients using deep-learning methods. A cohort comprising 5238 unique eyes classified as suspects or diagnosed with glaucoma was considered. All patients underwent ophthalmologic examination consisting of standard automated perimetry (SAP), macular OCT, and peri-papillary OCT on the same day. Deep learning models were trained to estimate G-pattern visual field (VF) mean deviation (MD) and cluster MD using retinal thickness maps from seven layers: retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer (GCL + IPL), inner nuclear layer and outer plexiform layer (INL + OPL), outer nuclear layer (ONL), photoreceptors and retinal pigmented epithelium (PR + RPE), choriocapillaris and choroidal stroma (CC + CS), total retinal thickness (RT). The best performance on MD prediction is achieved by RNFL, GCL + IPL and RT layers, with R2 scores of 0.37, 0.33, and 0.31, respectively. Combining macular and peri-papillary scans outperforms single modality prediction, achieving an R2 value of 0.48. Cluster MD predictions show promising results, notably in central clusters, reaching an R2 of 0.56. The combination of multiple modalities, such as optic-nerve-head circular B-scans and retinal thickness maps from macular SD-OCT images, improves the performance of MD and cluster MD prediction. Our proposed model demonstrates the highest level of accuracy in predicting MD in the early-to-mid stages of glaucoma. Objective measures recorded with SD-OCT can optimize the number of visual field tests and improve individualized glaucoma care by adjusting VF testing frequency based on deep-learning estimates of functional damage.

Two Cases of Ischemic Optic Neuropathy after Extracorporeal Membrane Oxygenation (ECMO)

Purpose: We report two cases of non-arteritic ischemic optic neuropathy (NAION) following extracorporeal membrane oxygenation (ECMO) treatment.Case summary: (Case 1) A 36-year-old man underwent ECMO treatment. Upon regaining consciousness, he complained of a darkened peripheral visual field and was subsequently referred to an ophthalmologist. His best-corrected visual acuity was 0.9 in the right eye and 0.8 in the left eye. The intraocular pressure measured 12 mmHg in the right eye and 10 mmHg in the left eye; color vision was normal. A visual field test demonstrated concentric visual field defects in both eyes, and a fundus examination revealed a pale optic disc. Optical coherence tomography (OCT) indicated a decrease in retinal nerve fiber layer (RNFL) thickness. (Case 2) A 48-year-old woman underwent ECMO treatment. After regaining consciousness, she reported decreased vision in her right eye. Her best-corrected visual acuity was limited to hand motion in the right eye and was 1.2 in the left eye. A relative afferent pupillary defect in the right eye was observed. Color vision in the right eye was compromised, and a fundus examination revealed a pale optic disc. A visual field test demonstrated total visual field defect in the right eye, while OCT showed decreases in both the RNFL thickness and the ganglion cell-inner plexiform layer thickness of the right eye. Magnetic resonance imaging (MRI) revealed high signal intensity and abnormal enhancement in the right retrobulbar optic nerve.Conclusions: In cases where vision loss and visual field defects are observed following ECMO treatment, differential diagnoses for ischemic optic neuropathy are warranted.