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Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head trauma. Brain pathology in CTE is characterized by neuronal loss, gliosis, and a distinctive pattern of neuronal accumulation of hyper-phosphorylated tau (p-tau) and phospho-TDP43 (p-TDP43). Visual anomalies have been reported by patients with CTE, but the ocular pathology underlying these symptoms is unknown. We evaluated retinal pathology in post-mortem eyes collected from 8 contact sport athletes with brain autopsy-confirmed stage IV CTE and compared their findings to retinas from 8 control patients without CTE and with no known history of head injury. Pupil-optic nerve cross sections were prepared and stained with hematoxylin and eosin (H&E), p-tau, p-TDP43, and total TDP43 by immunohistochemistry. No significant retinal degeneration was observed in CTE eyes compared to control eyes by H&E. Strong cytoplasmic p-TDP43 and total TDP43 staining was found in 6/8 CTE eyes in a subset of inner nuclear layer interneurons (INL) of the retina, while only 1/8 control eyes showed similar p-TDP43 pathology. The morphology and location of these inner nuclear layer interneurons were most compatible with retinal horizontal cells, although other retinal cell types present in INL could not be ruled out. No p-tau pathology was observed in CTE or control retinas. These findings identify novel retinal TDP43 pathology in CTE retinas and support further investigation into the role of p-TDP43 in producing visual deficits in patients with CTE.

ObjectiveTo investigate the confounding effect of nonexudative age-related macular degeneration (AMD), specifically drusen and outer retinal atrophy, on the architecture and automated segmentation of the inner retinal layers as measured with OCT.DesignObservational cross-sectional study.SubjectsTwo hundred sixty-three consecutive eyes with nonexudative AMD were identified through a retrospective chart review. Exclusion criteria were a diagnosis of glaucoma or glaucoma suspect, other retinal pathology affecting the macula, axial length > 26.5 mm or spherical equivalent less than -6 diopters, any other optic nerve or neurologic disorders, or poor image quality.MethodsDrusen were automatically segmented on macular OCT B-scans with a publicly available and validated deep learning approach. Automated segmentation of the inner plexiform layer (IPL)/inner nuclear layer (INL) boundary was carried out with the device's proprietary software.Main outcome measuresQuality of segmentation of the IPL/INL boundary as a function of drusen size and presence of inner retinal layer displacement in the area of macular pathology (drusen or atrophy).ResultsOne hundred twenty-five eyes (65 patients) met the inclusion criteria. Drusen size varied between 16 and 272 μm (mean, 118 μm). Automated segmentation had a 22% chance of failure if the drusen height was between 145 and 185 μm and was most likely to fail with drusen heights above 185 μm. When drusen height was normalized by total retinal thickness, segmentation failed 36% of the time when the drusen to total retinal thickness ratio was 0.45 or above. Images were likely to show displacement of inner retinal layers with drusen heights above 176 μm and a normalized drusen height ratio of 0.5 or higher. Eighty-seven percent of images with outer retinal atrophy displayed incorrect segmentation.ConclusionsOuter retinal diseases can alter the retinal topography and affect the segmentation accuracy of the inner retinal layers. Large drusen may cause segmentation error and compression of the inner macular layers. Geographic atrophy confounds automated segmentation in a high proportion of eyes. Clinicians should be cognizant of the effects of outer retinal disease on the inner retinal layer measurements when interpreting the results of macular OCT imaging in patients with glaucoma.

Background: Activation of the trigeminal vascular system in migraine releases vasoactive neurotransmitters, causing abnormal vasoconstriction, which may affect the ocular system, leading to retinal damage. The purpose of our study was to determine whether there are differences in each retinal layer between migraine patients and healthy subjects. Methods: A case-control study recruited 38 migraine patients and 38 age- and sex-matched controls. Optical coherence tomography was used to measure the thickness of the peripapillary and macular retinal nerve fiber layer (pRNFL and mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL). Results: The mean ages of the migraine patients and controls were 36.29 ± 9.45 and 36.45 ± 9.27 years, respectively. Thirty-four patients (89.48%) in both groups were female. The mean disability score was 19.63 ± 20.44 (indicating severe disability). The superior-outer INL of migraine patients were thicker than controls. Thickness of the GCL at temporal-outer sector and mRNFL at the superior-outer sector of the headache-side eyes was reduced. However, the INL of the headache-side-eye showed negative correlation with the disability score. This is the first study having found thinning of the GCL and mRNFL of the headache-side eyes. The INL was also thickened in migraines but showed negative correlation with the disability score. Conclusions: Increased INL thickness in migraine patients may result from inflammation. The more severe cases with a high disability score might suffered progressive retinal neuronal loss, resulting in thinner INL than less severe cases. [ABSTRACT FROM AUTHOR]

Optic Atrophy (OA) can be associated with the development of microcystic macular edema (MME) in the perifoveal retinal inner nuclear layer (INL). We aimed here to retrospectively determine the prevalence of MME in patients with non-glaucomatous OA in our tertiary ophthalmology department between 2015 and 2020. We then examined how MME affected the thicknesses of the different retinal layers and the differences in demographic and clinical characteristics between those patients who developed MME and those who did not. A total of 643 eyes (429 patients) were included (mean age 45.9 ± 17.8 years, 52% female). MME developed in 95 (15%) eyes and across all etiologies of OA except for toxic/nutritional causes, but the prevalence of MME varied between the different etiologies. The development of MME was associated with thinning of the ganglion cell layer (11.0 vs. 9.6 μm; p = 0.001) and the retinal nerve fiber layer (10.1 vs. 9.15 μm; p = 0.024), with INL thickening in the 3- and 6-mm diameter areas of the central fovea. Patients developing MME had significantly worse distance best-corrected visual acuity than those not developing MME (0.62 vs. 0.38 logMAR; p = 0.002). Overall, the presence of MME in OA cannot be used to guide the diagnostic work-up of OA.

Background Activation of the trigeminal vascular system in migraine releases vasoactive neurotransmitters, causing abnormal vasoconstriction, which may affect the ocular system, leading to retinal damage. The purpose of our study was to determine whether there are differences in each retinal layer between migraine patients and healthy subjects. Methods A case-control study recruited 38 migraine patients and 38 age- and sex-matched controls. Optical coherence tomography was used to measure the thickness of the peripapillary and macular retinal nerve fiber layer (pRNFL and mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL). Results The mean ages of the migraine patients and controls were 36.29 ± 9.45 and 36.45 ± 9.27 years, respectively. Thirty-four patients (89.48%) in both groups were female. The mean disability score was 19.63 ± 20.44 (indicating severe disability). The superior-outer INL of migraine patients were thicker than controls. Thickness of the GCL at temporal-outer sector and mRNFL at the superior-outer sector of the headache-side eyes was reduced. However, the INL of the headache-side-eye showed negative correlation with the disability score. This is the first study having found thinning of the GCL and mRNFL of the headache-side eyes. The INL was also thickened in migraines but showed negative correlation with the disability score. Conclusions Increased INL thickness in migraine patients may result from inflammation. The more severe cases with a high disability score might suffered progressive retinal neuronal loss, resulting in thinner INL than less severe cases.

Abstract Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head trauma. Brain pathology in CTE is characterized by neuronal loss, gliosis, and a distinctive pattern of neuronal accumulation of hyper-phosphorylated tau (p-tau) and phospho-TDP43 (p-TDP43). Visual anomalies have been reported by patients with CTE, but the ocular pathology underlying these symptoms is unknown. We evaluated retinal pathology in post-mortem eyes collected from 8 contact sport athletes with brain autopsy-confirmed stage IV CTE and compared their findings to retinas from 8 control patients without CTE and with no known history of head injury. Pupil-optic nerve cross sections were prepared and stained with hematoxylin and eosin (H&E), p-tau, p-TDP43, and total TDP43 by immunohistochemistry. No significant retinal degeneration was observed in CTE eyes compared to control eyes by H&E. Strong cytoplasmic p-TDP43 and total TDP43 staining was found in 6/8 CTE eyes in a subset of inner nuclear layer interneurons (INL) of the retina, while only 1/8 control eyes showed similar p-TDP43 pathology. The morphology and location of these inner nuclear layer interneurons were most compatible with retinal horizontal cells, although other retinal cell types present in INL could not be ruled out. No p-tau pathology was observed in CTE or control retinas. These findings identify novel retinal TDP43 pathology in CTE retinas and support further investigation into the role of p-TDP43 in producing visual deficits in patients with CTE.

PurposeWe aimed to investigate non-exudative microcystoid macular abnormalities for visual and anatomical outcome in patients with retinal vein occlusion (RVO) with and without glaucomatous optic neuropathy (GON).MethodsMedical records of 124 eyes (105 patients) with RVO were reviewed and analyzed. Eyes demonstrating microcystoid macular abnormalities were divided into 2 groups, those with evidence of glaucoma (group A) and those without glaucoma (group B). Best-corrected visual acuity (BCVA), the prevalence and number of microcystoid macular abnormalities, and number of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections were compared at baseline and follow-up.ResultsSeventy-one out of 105 eyes (67.6%) with RVO displayed microcystoid macular abnormalities. Thirty-eight out of 71 eyes (53.5%) presented with concomitant glaucoma (group A), while the remaining 33 eyes (42.6%) had no history of glaucoma (group B). At the end of the follow-up period, mean BCVA was worse in group A versus group B (20/80 versus 20/40, respectively; p = .003). The mean number of anti-VEGF injections was 10.1 ± 9.2 in group A versus 5.9 ± 6.9 in group B (p = .03).ConclusionEyes with RVO and concomitant glaucoma exhibited a significantly higher number of microcystoid macular abnormalities and worse BCVA versus eyes with RVO without glaucoma.

Purpose: to assess the tomographic retinal layers' thickness in eyes affected by branch retinal artery occlusion (BRAO) and to compare it to those of patients affected by primary open angle glaucoma (POAG). Methods: retrospective review of 27 patients; 16 with BRAO (16 eyes) and 11 with POAG (20 eyes) were identified among those who received SD-OCT scans, including analysis of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), neuroretinal rim (NRR), circumpapillary RNFL at 3.5 mm and hemisphere asymmetry (HA). Results: the total IPL and INL thinning difference between the two groups was statistically significant (p = 0.0067 and p < 0.0001, respectively). The HA difference for the total macular thinning, mRNFL, GCL, IPL and INL (p < 0.0001) was also statistically significant. The analysis of the average total retinal thinning, total mRNFL and GCL thinning showed no statistically significant difference between the two groups. Conclusions: unilateral inner retinal thinning may represent a sign of temporal BRAO, particularly for INL thinning and HA difference over 17µm in total retinal layer thinning. This information is particularly useful in the diagnosis of previous, undiagnosed BRAO and may help prevent further retinal arterial occlusion and possible cerebrovascular incidents. [ABSTRACT FROM AUTHOR]

IntroductionCongenital X-linked retinoschisis (XLRS) presents as macular retinoschisis/degeneration in almost all patients and as peripheral retinoschisis in half the patients. Although the optical coherence tomography (OCT) findings of macular retinoschisis have been well investigated, those of peripheral retinoschisis have rarely been reported. This study aimed to report the ultra-widefield OCT findings of the peripheral retina in patients with XLRS.MethodsMedical records of 10 Japanese patients (19 eyes) with clinically and/or genetically diagnosed XLRS were retrospectively reviewed. Funduscopic, electroretinographic, and OCT findings were reviewed and evaluated. Some were also genetically evaluated for the RS1 gene.ResultsOCT of the macula revealed schises and/or cystoid changes in the inner nuclear layer (INL) and outer nuclear layer. In contrast, OCT of the peripheral retina revealed schises and/or cystoid changes in the INL in eight eyes (44%), and/or splitting in the ganglion cell layer (GCL) in 10 (56%) of the 18 eyes with clear OCT images. No schisis or cystoid changes were found in the peripheral OCT images of eight eyes (44%). A 16-year-old boy presented with retinal splitting of the GCL and INL of the inferior retina, although he had no ophthalmoscopic peripheral retinoschisis. Genetic examinations were performed on three patients, all of whom had reported missense mutations in the RS1 gene.ConclusionIn XLRS, peripheral bullous retinoschisis results from GCL splitting in the retina. One of the 10 patients with XLRS showed intraretinal retinoschisis in the GCL in the inferior periphery, which was unremarkable on ophthalmoscopy (occult retinoschisis). Although both peripheral bullous retinoschisis and occult retinoschisis showed splitting/cystic changes in the GCL, further studies are needed to determine whether occult retinoschisis progresses to bullous retinoschisis.

Purpose: To investigate the relationship between retinal traction force and impairment of the inner retinal layer in patients with epiretinal membrane (ERM). Design: Nonrandomized, retrospective consecutive case series. Participants: Two hundred nine eyes of 201 patients with idiopathic ERM who underwent vitrectomy for idiopathic ERM were enrolled. Methods: Retinal folds caused by ERM were visualized using en face OCT, and the maximum depth of retinal folds within the parafovea (MDRF) was measured. Focal macular electroretinogram (ERG) was used to measure the amplitude and implicit time of each component for the ERM eyes and the normal fellow eyes. B-scan OCT images were used to measure the thicknesses of the inner nuclear layer (INL) and outer nuclear layer (ONL) + outer plexiform layer (OPL). Expression of α-smooth muscle actin (α-SMA) in surgically removed ERM specimens was quantified by reverse-transcription polymerase chain reaction. Main Outcome Measures: We analyzed the relationship between MDRF and the relative amplitudes of focal macular ERG (affected eye/fellow eye), the relationships between MDRF and the mean INL thickness and ONL+OPL thickness, comparison of INL thickness and ONL+OPL thickness for each area when cases were classified according to MDRF localization in the ETDRS chart, and the relationship between MDRF and the relative expression of α-SMA in the ERM specimens. Results: The MDRF significantly correlated with the relative amplitudes (affected eye/fellow eye) of b-waves and oscillatory potentials (r = −0.657, P = 0.015; r = −0.569, P = 0.042, respectively) and the mean INL thickness and ONL+OPL thickness (r = 0.604, P

To report the clinical and imaging findings of 4 patients with benign intraretinal tumors, 2 of which were associated with retinal pigment epithelium (RPE) hypertrophy. To our knowledge, this condition has not been described previously and should be distinguished from retinoblastoma and other malignant retinal neoplasms. Retrospective case series. Four patients from 3 institutions. Four patients with intraretinal tumors of the inner nuclear layer (INL) underwent a combination of ophthalmic examination, fundus photography, fluorescein angiography, OCT, OCT angiography, and whole exome sequencing. Description of multimodal imaging findings and systemic findings from 4 patients with benign intraretinal tumors and whole exome studies from 3 patients. Six eyes of 4 patients 5, 13, 32, and 27 years of age were found to have white intraretinal tumors that remained stable over the follow-up period (range, 9 months–4 years). The tumors were unilateral in 2 patients and bilateral in 2 patients. The tumors were white, centered on the posterior pole, and multifocal, with some consisting of multiple lobules with arching extensions that extended beyond the central tumor mass. OCT demonstrated these lesions to be centered within the INL at the border of the inner plexiform layer. In addition, 2 patients demonstrated congenital hypertrophy of the RPE (CHRPE) lesions. Three of 4 patients underwent whole exome sequencing of the blood that revealed no candidate variants that plausibly could account for the phenotype. We characterize a novel benign tumor of the INL that, in 2 patients, was associated with separate CHRPE lesions. We propose the term benign lobular inner nuclear layer proliferation to describe these lesions. Proprietary or commercial disclosure may be found after the references. [ABSTRACT FROM AUTHOR]

Purpose: to assess the tomographic retinal layers’ thickness in eyes affected by branch retinal artery occlusion (BRAO) and to compare it to those of patients affected by primary open angle glaucoma (POAG). Methods: retrospective review of 27 patients; 16 with BRAO (16 eyes) and 11 with POAG (20 eyes) were identified among those who received SD-OCT scans, including analysis of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), neuroretinal rim (NRR), circumpapillary RNFL at 3.5 mm and hemisphere asymmetry (HA). Results: the total IPL and INL thinning difference between the two groups was statistically significant (p = 0.0067 and p < 0.0001, respectively). The HA difference for the total macular thinning, mRNFL, GCL, IPL and INL (p < 0.0001) was also statistically significant. The analysis of the average total retinal thinning, total mRNFL and GCL thinning showed no statistically significant difference between the two groups. Conclusions: unilateral inner retinal thinning may represent a sign of temporal BRAO, particularly for INL thinning and HA difference over 17µm in total retinal layer thinning. This information is particularly useful in the diagnosis of previous, undiagnosed BRAO and may help prevent further retinal arterial occlusion and possible cerebrovascular incidents.

PurposeCotton Wool Spots (CWS) are a commonly described retinal finding in the posterior segment associated with an extensive number of systemic diseases. The appearance of a CWS in the setting of glaucoma has rarely been reported and has not been correlated with pathology to localized loss of the nerve fiber layer previously. In this case report, we augment a previous report of an 18 year old female with a diagnosis of low grade ciliary body melanoma. This patient experienced eventual mechanical angle closure with a CWS appearing in the posterior pole in the setting of acute elevation of intraocular pressure (IOP). This eye underwent enucleation and pathology evaluation.ObservationsFundus photography documented a CWS in the posterior segment during a period of acute elevation in IOP. Subsequently the eye was enucleated due to pain from refractory angle closure glaucoma secondary to low grade iris-ciliary body ring melanoma. The specific site of the prior CWS was studied with 1μ Epon retinal step sections stained with a novel AgNO3 solution. Light microscopy demonstrated a retinal nerve fiber layer scar and inner nuclear layer collapse in the prior location of the CWS. Light microscopy and transmission electron microscopy shortly after enucleation had demonstrated temporal quadrant laminar optic nerve (ON) retrograde axonal transport block.Conclusions and importanceAlthough not commonly associated with glaucoma, CWS can present in the setting of acute elevations of IOP and may be associated with loss of nerve fiber layer. This loss of nerve fiber layer can confound the ability to judge glaucoma progression based on nerve fiber layer thickness via optical coherence tomography and changes in disc contours. Patient care may benefit from care provider's awareness of this possible phenomenon in the setting of angle closure.

Background: Ocrelizumab was found to decrease brain atrophy rate in primary progressive multiple sclerosis (PPMS), but no data are currently available on the effect of ocrelizumab on retinal layer thicknesses in the PPMS population. Objective: To assess retinal layer changes in ocrelizumab-treated PPMS and test their possible application as biomarkers of therapy response. Methods: 36 PPMS patients, treated with ocrelizumab for at least 6 months, and 39 sex- and age-matched healthy controls (HC) were included in a blind, longitudinal study. Spectrum-domain optical coherence tomography (SD-OCT) was performed at study entry (T0) and after 6 (T6) and 12 months (T12). At month 24 (T24), patients were divided into responders (no evidence of 1-year confirmed disability progression, 1y-CDP) and non-responders (evidence of 1y-CDP). Results: At T24, 23/36 (64%) patients were considered responders and 13/36 (36%) non-responders. At T0, peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell–inner plexiform layer (GCIPL) and inner retinal layer (IRL) volume were significantly lower in PPMS compared to HC (p = 0.001 for all comparisons). At T6 and T12, non-responders significantly differed in the inner nuclear layer (INL) thinning rate compared to responders (p = 0.005 at both time-points). Conclusions: Ocrelizumab significantly slows down INL thinning rate in PPMS responders. The longitudinal analysis of retina layer changes by means of OCT may be a promising prognostic test, and merits further investigations. [ABSTRACT FROM AUTHOR]

Objective: To assess axonal and neuronal damage of the retina in patients with familial (fMS) and sporadic multiple sclerosis (sMS). Methods: 87 relapsing-remitting MS patients (45 patients with sMS, 42 patients with fMS) and 30 healthy controls were included in the study. Optical coherence tomography (OCT) was performed with the spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering, Germany). The peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, total macular volume (TMV) and the inner nuclear layer (INL) thickness were measured. Results: A significant reduction of the pRNFL thickness was detected in sMS and fMS compared to the control group (86.29 (+/- 16.13) μm in sMS, 84.78 (+/- 12.92) μm in fMS, 98.93 (+/- 6.71) μm in control group; p < 0.001). There was no significant difference in the pRNFL thickness between sMS and fMS (p = 0.5239). The GCIPL thickness was significantly decreased in sMS and fMS compared to the control group [66.0581 (+/- 11.2674) μm in sMS, 63.8386 (+/-10.004) μm in fMS, 76.5074 (+/- 5.0004) μm in control group; p < 0.001]. A significant reduction of the TMV was shown in sMS and fMS compared to the control group [8.4541(+/- 0.4727) mm3 in sMS, 8.3612 (+/- 0.4448) mm3 in fMS, 8.8387 (+/- 0.314) mm3 in control group; p < 0.0011]. No difference in the GCIPL thickness and TMV between sMS and fMS was found (p = 0.3689 and p = 0.3758, respectively). The INL thickness in sMS and fMS did not differ compared to the control group [34.2323 (+/- 2.7006) μm in sMS, 34.5159 (+/- 2.9780) μm in fMS, 33.6148 (+/- 2.0811) μm in control group; p = 0.5971 and p = 0.1870, respectively] and between the two forms (p = 0.4894). Conclusion: We confirmed the presence of axonal and neuronal damage of the retina in sMS and fMS. Both forms of MS did not differ significantly from each other with respect to RFNL, GCIPL, MV and INL. ON induced significant reduction of the pRNFL, GCIPL and MV in both groups of pwMS. [ABSTRACT FROM AUTHOR]

Purpose: Report the clinical and imaging findings of a patient with an intraretinal benign tumor that was documented as an unexpected clinical finding after an ischemic stroke in the context of mitral valve disease. This tumor must be distinguished from retinoblastoma and other malignant neoplasms., Methods: A patient with intraretinal tumor of the inner nuclear layer (INL) underwent a combination of ophthalmic examination, fundus photography, fluorescein angiography, optical coherence tomography (OCT), and optical coherence tomography angiography (OCT-A)., Results: A 64-year-old male patient with unilateral benign tumor lesions dependent on the internal retina, centered in the posterior pole, and multifocal. OCT showed that these lesions were centered within the INL at the edge of the inner plexiform layer and were not associated with other findings in the posterior pole., Conclusions: Benign Lobular Inner Nuclear Layer Proliferations (BLIP) of the Retina are recently described lesions that should be considered, given their distinctive characteristics that set them apart from other benign and malignant retinal lesions., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Microcystoid macular degeneration (MMD) is a condition where cystoid vacuoles develop within the inner nuclear layer of the retina in humans in a variety of disorders. Here we report the occurrence of MMD in non-human primates (NHPs) with various retinal ganglion cell (RGC) pathologies and evaluate the hypothesis that MMD does not precede RGC loss but follows it., Methods: Morphological studies were performed of the retinas of NHPs, specifically both rhesus ( Macaca mulatta ) and cynomolgus macaques ( Macaca fascicularis ), in which MMD was identified after induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and spontaneous idiopathic bilateral optic atrophy. In vivo imaging analyses included fundus photography, fluorescein angiography (FA), optical coherence tomography (OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), light microscopy, and electron microscopy., Results: MMD, like that seen on OCT scans of humans, was found in both rhesus and cynomolgus macaques with EG. Of 13 cynomolgus macaques with chronic EG imaged once with OCT six of 13 animals were noted to have MMD. MMD was also evident in a cynomolgus macaque with bilateral optic atrophy. Following HEA, MMD did not develop until at least 2 weeks following the RNFL loss., Conclusion: These data suggest that MMD may be caused by a retrograde trans-synaptic process related to RGC loss. MMD is not associated with inflammation, nor would it be an independent indicator of drug toxicity per se in pre-clinical regulatory studies. Because of its inconsistent appearance and late development, MMD has limited use as a clinical biomarker.

Optic Atrophy (OA) can be associated with the development of microcystic macular edema (MME) in the perifoveal retinal inner nuclear layer (INL). We aimed here to retrospectively determine the prevalence of MME in patients with non-glaucomatous OA in our tertiary ophthalmology department between 2015 and 2020. We then examined how MME affected the thicknesses of the different retinal layers and the differences in demographic and clinical characteristics between those patients who developed MME and those who did not. A total of 643 eyes (429 patients) were included (mean age 45.9 ± 17.8 years, 52% female). MME developed in 95 (15%) eyes and across all etiologies of OA except for toxic/nutritional causes, but the prevalence of MME varied between the different etiologies. The development of MME was associated with thinning of the ganglion cell layer (11.0 vs. 9.6 μm; p = 0.001) and the retinal nerve fiber layer (10.1 vs. 9.15 μm; p = 0.024), with INL thickening in the 3- and 6-mm diameter areas of the central fovea. Patients developing MME had significantly worse distance best-corrected visual acuity than those not developing MME (0.62 vs. 0.38 logMAR; p = 0.002). Overall, the presence of MME in OA cannot be used to guide the diagnostic work-up of OA.

ObjectiveTo assess axonal and neuronal damage of the retina in patients with familial (fMS) and sporadic multiple sclerosis (sMS).Methods87 relapsing-remitting MS patients (45 patients with sMS, 42 patients with fMS) and 30 healthy controls were included in the study. Optical coherence tomography (OCT) was performed with the spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering, Germany). The peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, total macular volume (TMV) and the inner nuclear layer (INL) thickness were measured.ResultsA significant reduction of the pRNFL thickness was detected in sMS and fMS compared to the control group (86.29 (+/- 16.13) μm in sMS, 84.78 (+/- 12.92) μm in fMS, 98.93 (+/- 6.71) μm in control group; p < 0.001). There was no significant difference in the pRNFL thickness between sMS and fMS (p = 0.5239). The GCIPL thickness was significantly decreased in sMS and fMS compared to the control group [66.0581 (+/- 11.2674) μm in sMS, 63.8386 (+/-10.004) μm in fMS, 76.5074 (+/- 5.0004) μm in control group; p < 0.001]. A significant reduction of the TMV was shown in sMS and fMS compared to the control group [8.4541(+/- 0.4727) mm3 in sMS, 8.3612 (+/- 0.4448) mm3 in fMS, 8.8387 (+/- 0.314) mm3 in control group; p < 0.0011]. No difference in the GCIPL thickness and TMV between sMS and fMS was found (p = 0.3689 and p = 0.3758, respectively). The INL thickness in sMS and fMS did not differ compared to the control group [34.2323 (+/- 2.7006) μm in sMS, 34.5159 (+/- 2.9780) μm in fMS, 33.6148 (+/- 2.0811) μm in control group; p = 0.5971 and p = 0.1870, respectively] and between the two forms (p = 0.4894).ConclusionWe confirmed the presence of axonal and neuronal damage of the retina in sMS and fMS. Both forms of MS did not differ significantly from each other with respect to RFNL, GCIPL, MV and INL. ON induced significant reduction of the pRNFL, GCIPL and MV in both groups of pwMS.

To describe a case of stellate nonhereditary idiopathic foveomacular retinoschisis in a middle-aged woman and to define the structural and angiographic data of vascular and perfusion density. Spectral-domain optical coherence tomography was able to detect a unilateral idiopathic retinoschisis, revealing a stellate pattern of retinal concentric cysts, and optical coherence tomography angiography revealed minimal changes in vascular and perfusion density metrics. There were consistent FA findings with almost unaltered foveal changes. Multifocal electroretinography depicted a subtle reduction of dark-adapted a-wave and b-wave amplitudes. This fortuitous case gives a window on the importance of a routine specialized ophthalmic examination. Purpose: To describe a case of stellate nonhereditary idiopathic foveomacular retinoschisis in a middle-aged woman and to depict the classic retinal fluorangiography (FA) findings, structural characteristics using macular spectral-domain optical coherence tomography angiographic data of vascular and perfusion density using optical coherence tomography angiography (OCT-A), and standardized multifocal electroretinography (mfERG) findings. Methods: This is a case report of a 53-year-old ophthalmologist who was incidentally diagnosed with unilateral idiopathic foveomacular retinoschisis. Stellate nonhereditary idiopathic foveomacular retinoschisis is defined as a foveal elevation without alternative explanation for retinoschisis. FA, spectral-domain optical coherence tomography, optical coherence tomography angiography, and multifocal electroretinography were used as tools to obtain an integral multimodal diagnosis of this entity. Results: Clinical examination and multimodal imaging were able to detect unilateral idiopathic retinoschisis, revealing a stellate pattern of retinal concentric cysts with minimal changes in vascular and perfusion density metrics and confirming the absence of bridging vessels. There were consistent FA findings, with almost unaltered foveal changes. Multifocal electroretinography depicted a subtle reduction in dark-adapted a-wave and b-wave amplitudes. Conclusion: Improvements and innovations in technology for ophthalmic diagnosis have revolutionized our capacity for diagnostic decision-making. Spectral-domain optical coherence tomography and optical coherence tomography angiography are useful tools for diagnosis and follow-up assessment. This fortuitous case gives a window on the importance of a routine specialized ophthalmic examination and how multimodal imaging can depict important and specific findings not evident from a clinical point of view. The subtle but important changes observed in optical coherence tomography angiography and multifocal electroretinography will help better define this clinical entity. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlations of thickness of three retinal layers with retinal displacement after idiopathic macular hole surgery. Study design: Retrospective, consecutive, case series. Methods: 42 eyes of 42 patients undergoing macular hole surgery with internal limiting membrane peeling were studied. Retinal distance was measured with near-infrared images between the optic nerve and the intersection of retinal vessels at four quadrants. Retinal thicknesses of inner retinal layer, inner nuclear layer and outer retinal layer were measured 1000 μm away from the central fovea using Spectralis. Results: Retinal distances other than the nasal quadrant decreased postoperatively (p < 0.001). Retinal displacement (%) correlated significantly with the change in inner nuclear layer thickness in the temporal sector at 1, 3, and 6 months, in the superior sector at 2 weeks, 1, and 6 months, and in the inferior sector at 3 and 6 months postoperatively (r = 0.319–0.570, p < 0.001–0.040), but not in the inner or outer retinal layers. Conclusion: Internal limiting membrane peeling for macular hole enhances retinal displacement toward the optic disc, whose distances correlate with the changes in inner nuclear layer thickness. [ABSTRACT FROM AUTHOR]

AIM: To investigate the morphology and electrophysiological properties of neurons in the inner nuclear layer(INL)of the adult rat retina slices. The retinal slices were prepared by low-melt agarose embedding and then cutted by vibratome. METHODS: Whole cell patch clamp and intracellular staining with Lucifer Yellow were used in this study to study the morphology and electrophysiological properties of the INL neurons in retinal slices.RESULTS: Retinal slices prepared in this method possessed a very smooth surface. The cells on the retinal slices maitained very good vitality, and some of the cells even retained their dendritic connections with other cells on the slice. According to the size and location of the cell bodies, neurons in the INL were easy to differentiate. Luciifer Yellow contained in the intracellular solution revealed the morphology of the recorded cell very well. Bipolar cells possessed elongated cell bodies and their processes mainly extended along the vertical direction. Horizontal cells and amacrine cells possessed much bigger and round cell bodies, resided in the outermost and inner most of the INL, respectively. The rest membrane potential and membrane capacitance of horizontal cell and amacrine cell were much higher than that of bipolar cells. Under a voltage step from -60mV to +40mV, 10mV per step, 41.7% of the cone bipolar cells and 64.7% of the amacrine cells exhibited inward sodium current and outward potassium current. Other cells only possessed outward potassium current. CONCLUSION: The method of preparing retinal slices was very simple, and the viability of the slices were stable. These facilitated the patch-clamp recording of all the neurons in the INL including horizontal cells. Further investigation of the electrophysiological properties of the neurons in the INL was essential in revealing the mechanism of vision.

Purpose: To compare intraretinal layers between the eyes in patients with myopic anisometropia, and evaluate the relationship between the layers with spherical equivalent (SE) and axial length (AL). Methods: In this retrospective study, the more myopic (MM) and fellow (F) eyes of 41 patients with myopic anisometropia, and 38 emmetropic (± 0.50 diopter) control (C) eyes were inclueded. Intraretinal layer segmentation was performed by optical coherence tomography. Global volumes of retinal layers and their thicknesses in nine macular regions were compared. Correlation analysis was used to determine the relationship with SE and AL in each layer. Results: Total retinal, ganglion cell (GCL), inner nuclear (INL), and outer plexiform (OPL) layer volumes in MM eyes were less than in C eyes, while INL and OPL were less than in F eyes. There was no difference in the fovea, except for the retinal pigment epithelium. In MM eyes, only INL and OPL were thin in at least one perifoveal and parafoveal quadrant compared to F eyes. Only INL and OPL thicknesses were significantly correlated with both SE and AL in all perifoveal quadrants. In contrast to the thinning found in MM eyes, the only layer in which thickening was detected to compare to C eye was nerve fiber layer (NFL), which correlated positively with SE and negatively with AL. Conclusion: While the fovea is less affected by myopia, thinning becomes remarkable in the perifoveal quadrants. Despite thinning in many layers, especially INL and OPL, NFL thickening may be seen due to myopia. [ABSTRACT FROM AUTHOR]

Quantification of retinal atrophy, caused by therapeutics and/or light, by manual measurement of retinal layers is labor intensive and time-consuming. In this study, we explored the role of deep learning (DL) in automating the assessment of retinal atrophy, particularly of the outer and inner nuclear layers, in rats. Herein, we report our experience creating and employing a hybrid approach, which combines conventional image processing and DL to quantify rodent retinal atrophy. Utilizing a DL approach based upon the VGG16 model architecture, models were trained, tested, and validated using 10,746 image patches scanned from whole slide images (WSIs) of hematoxylin-eosin stained rodent retina. The accuracy of this computational method was validated using pathologist annotated WSIs throughout and used to separately quantify the thickness of the outer and inner nuclear layers of the retina. Our results show that DL can facilitate the evaluation of therapeutic and/or light-induced atrophy, particularly of the outer retina, efficiently in rodents. In addition, this study provides a template which can be used to train, validate, and analyze the results of toxicologic pathology DL models across different animal species used in preclinical efficacy and safety studies. [ABSTRACT FROM AUTHOR]

The primary aim of the study was to investigate the effects of anti-vascular endothelial growth factor (VEGF) injections on the inner retinal layer anatomy of the lesion-free retina in eyes treated for neovascular age-related macular degeneration (nAMD). The secondary aim was to compare the changes of inner retinal layers in the lesion-free region of treated eyes with the same region of the untreated, fellow eyes and, thus, to elucidate any adverse effect of anti-VEGF treatments independently of 1-year aging changes. This was a retrospective, longitudinal, case–control study of 50 eyes of 25 patients. Twenty-five eyes with nAMD comprised the study group (16 eyes treated with aflibercept and 9 eyes treated with ranibizumab) and 25 fellow eyes with dry AMD (16 eyes in AREDS 2 and 9 eyes in AREDS 3) comprised the fellow eye group. Spectral-domain optical coherence tomography (SD-OCT) measurements were done at pre-treatment, 1 month after three loading anti-VEGF injections and at the end of 1 year. The retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL) thicknesses and total retinal thickness in the macula were measured. Thicknesses of inner retinal layers which were lesion-free in the outer nasal subfield of ETDRS grid were analysed and the changes in thicknesses during the follow-up period were compared between study and fellow eye groups. Paired t-test for normally distributed variables was applied for analyses of differences for the comparison of the results across the pre-and the post-. A p value of less than 0.05 was considered statistically significant. The mean number of injections was 5.76 ± 1.26 in the study group in 1 year. The mean decrease in total retinal thickness was significant with 6.08 ± 9.05 µm (p= 0.003) in nAMD group and was insignificant with 0.32 ± 1.03 µm (p> 0.05) in fellow eye group with dry AMD. Most of the retinal thickness decrease was during first three injections in nAMD group. Total retinal thickness and GCL thickness were thinner in the study group at every follow-up examination, but the difference between groups was not statistically significant (p> 0.05). RNFL, GCL, IPL, and INL thicknesses did not demonstrate a statistically significant change in both study and fellow eye groups during 1 year follow-up period (p> 0.05). Repeated anti-VEGF injections in nAMD appear to have no significant effect on the RNFL, GCL, IPL, and INL thicknesses of the lesion-free retina. Additionally, there was no significant difference in inner retinal layer changes between in eyes treated with anti-VEGF injections for nAMD and fellow eye group during 1-year follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Over the past few years, the incidence of retinal ischemic disorders has been increasing, due to a rising prevalence of such socially burdensome diseases as diabetes and hypertension, which ultimately lead to ocular vascular pathology. The identification of new treatment options that would prevent retinal neuron death is a crucial task of modern pharmacology. Materials and methods: The research was carried out on male Wistar rats. Retinopathy was modeled by inducing a 30-min ischemic episode, with a 72-hour period of reperfusion and subsequent administration of Retinalamin and Emoxypine for 10 days. The effectiveness of the drugs was evaluated by electroretinographic, ophthalmoscopic and morphological assessments. Results and discussion: On Day 14 of the experiment, a dose-dependent preservation of the electroretinogram b-wave/a-wave amplitude ratio was observed in the animals treated with Retinalamin depending on a dose (1.39±0.06, 1.46±0.03 and 1.49±0.04 in low (0.214 mg/kg), medium (0.428 mg/kg) and high (0.857 mg/kg) Retinalamin dose groups, respectively). The ophthalmoscopic picture of the fundus oculi also improved following the treatment with Retinalamin (1.42, 1.69 and 1.90 times lower ophthalmoscopic scores compared to placebo-treated animals in low, medium and high dose groups, respectively). The morphologic "coefficient of change" applied to ganglion cell layer was 2.2, 1.7 and 1.6 points in low, medium and high dose Retinalamin groups, respectively. These results are significantly different from both intact and placebo group (p<0.05). Based on the aforementioned experimental findings, we conclude that Retinalamin has a retinoprotective effect and is superior to the drug of comparison (Emoxypine). Conclusion: The greatest neuroprotective effects were shown in the groups receiving Retinalamin. In these groups, the ERG b-wave/a-wave amplitude ratio was preserved, the ophthalmoscopic picture was less pathologic and retinal morphology features were close to those of the intact retina. [ABSTRACT FROM AUTHOR]

Background: Retinal inner nuclear layer (INL) and olfactory threshold (OT) are associated with inflammatory activity in multiple sclerosis (MS). Objective: The study aims to investigate (a) whether there is an association of INL and OT in MS and (b) if changes in INL and OT follow a time pattern in relation to MS relapse. Methods: We assessed INL by optical coherence tomography and OT by Sniffin' Sticks in three different cohorts: a cross-sectional MS cohort (n = 260), a longitudinal, 3-year cohort of MS (n = 141) and healthy controls (n = 30), and a longitudinal, 24-weeks cohort with acute MS relapse (n = 28) and stable MS controls (n = 27). Results: Cross-sectionally, INL and OT were strongly correlated with number but not localization of relapse in the previous 12 months and INL correlated with OT. Longitudinally, INL was thicker and OT score was lower short term in times of relapse activity, but not long term and independent of relapse localization. In acute MS relapse, INL and OT were altered compared with stable MS, again, independent of relapse localization resolving over 12–24 weeks with faster approximation to stable MS after escalation of disease-modifying treatment. Conclusions: INL and OT are interlinked markers of short-term inflammatory activity, following a nearly congruent time pattern and independent of relapse localization, possibly reflecting a proinflammatory state within the central nervous system. [ABSTRACT FROM AUTHOR]

In the visual pathway of patients with multiple sclerosis (MS), the inner nuclear layer (INL) of the retina is a tight barrier for retrograde trans-synaptic degeneration. In this observational, retrospective cross-sectional study, segmented macular spectral domain optical coherence tomography (OCT) volume scans were reviewed to investigate if this observation also holds true for anterograde trans-synaptic degeneration. Significant thinning was found in all retinal layers in patients with outer retinal diseases compared with the healthy controls, while there was no significant attenuation of the outer retina in patients with MS. In contrast to the tight barrier function observed with retrograde trans-synaptic degeneration, the INL appears to be more permissive for the propagation of anterograde trans-synaptic degeneration. We speculate that this may be due to the size of the area affected and be explained by convergence and divergence of axons within the retinal layers. These findings are likely relevant to future restorative stem cell treatment of the outer retinal layers, as time may matter. [ABSTRACT FROM AUTHOR]

Background: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. Objective: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS.Methods In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre. Results: There was a significant increase in INL volume in eyes with new MSON during the study (N = 61/1562, β = 0.01 mm3, p < .001). Clinical relapses (other than MSON) were significantly associated with increased INL volume (β = 0.005, p = .025). INL volume was independent of disease progression (β = 0.002 mm3, p = .474). Conclusion: Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association of retinal fluid volume with the visual and anatomic outcomes of patients with diabetic macular edema (DME) after treatment with bevacizumab. Study design: Retrospective observational study. Methods: We retrospectively analyzed 65 eyes of 58 DME patients treated with bevacizumab. The volumes of the inner intraretinal fluid (IRF) in the inner nuclear layer (INL), outer IRF in the outer plexiform layer (OPL)/outer nuclear layer (ONL), and subretinal fluid (SRF) were calculated. The correlations between the baseline fluid volumes and best-corrected visual acuity (BCVA), area of disorganization of the retinal inner layers (DRIL), disrupted external limiting membrane (ELM), and disrupted ellipsoid zone (EZ) at 12 months after treatment were assessed. Results: The baseline volume of the inner IRF correlated with poor BCVA at the final visit (r = 0.52, P <.001) whereas the baseline volume of the outer IRF and SRF volume did not show a significant correlation with BCVA at the final visit (P =.07 and P =.61, respectively). The improvement in BCVA correlated with the reduction in the baseline volume of the inner IRF and outer IRF (r = 0.25, P =.04 and r = 0.36, P =.003), but not with the SRF volume (P =.59). The baseline volume of the inner IRF correlated positively with the area of DRIL and the disrupted ELM at the final visit (r = 0.56, P <.001 and r = 0.25, P =.04, respectively). Such relationship remained in each quadrant of the macula (P <.005 for all quadrants). Conclusion: The baseline volume of the inner IRF correlated with a poor visual outcome, an increased DRIL area, and a more disrupted ELM area in patients with DME after treatment with bevacizumab. [ABSTRACT FROM AUTHOR]

Abstract Circulating miR-96-5p, -124-3p, and 183-5p have been reported as safety biomarkers for retinal toxicity. In the present research, 5 serum microRNAs (miRNAs), which are highly specific to and abundant in the retina, including the 3 miRNAs previously mentioned, were assessed in 3 different models of retinal toxicity. Distinct types of retinal lesions were induced in rats by a single dose of N-methyl -N- nitrosourea (MNU: 10, 30, and 50 mg/kg, i.p.), N-methyl- d -aspartate (NMDA: 200 nmol/eye, intravitreal injection), or sodium iodate (NaIO 3 : 30 mg/kg, i.v.). Time-course change of serum miRNAs was evaluated by RT-PCR for up to 1 week after administration. Ophthalmologic and histologic examinations and electroretinogram recording were also performed. MNU at 50 mg/kg induced photoreceptor cell death, with elevation in serum miR-96-5p, -124-3p, and -183-5p levels. NMDA induced retinal ganglion and inner nuclear layer cell death, with elevation in serum miR-124-3p. In both models, serum miRNA elevations occurred in parallel with the onset of neuroretinal cell death and retinal dysfunction. NaIO 3 induced retinal pigment epithelial cell death without changes in neuroretinal cell or serum miRNAs. In the present research, circulating miR-124-3p was elevated in a case of retinal ganglion and inner nuclear layer cell death as well as photoreceptor cell death. Our data suggest that different patterns of circulating miRNA elevations correspond to death of a specific neuroretinal cell. A miRNA panel consisting of miR-96-5p, -124-3p, and -183-5p may be used as a biomarker to detect neuroretinal cell death and identify the specific target cell. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between the foveal avascular zone (FAZ) and the inner nuclear layer (INL)-free zone in the center of the fovea in order to provide an improved approach to evaluation of the FAZ area with optical coherence tomography angiography (OCTA).Methods: Thirty-six healthy individuals (36 eyes) and 15 age-matched patients (15 eyes) with nonproliferative diabetic retinopathy (nPDR) were included in this study. The FAZ, as well as INL-free zone, was measured on OCTA images. The FAZ area, INL-free zone area, and the ratio of the INL-free zone area to the FAZ area were compared between healthy subjects and nPDR patients.Results: The mean FAZ area in healthy subjects and nPDR patients was 0.33 ± 0.1 mm2 and 0.41 ± 0.19 mm2 (p < 0.05), respectively. The mean INL-free zone area in healthy subjects and nPDR patients was 0.33 ± 0.07 mm2 and 0.25 ± 0.09 mm2 (p > 0.05), respectively. The INL-free zone area to the FAZ area ratio in healthy subjects and nPDR patients was 1.08 ± 0.25 and 0.56 ± 0.18 (p < 0.001), respectively. Receiver operating characteristic analysis showed that the INL-free zone area to the FAZ area ratio had a higher area under curve (0.94; 80.0% sensitivity and 97.2% specificity) compared to the FAZ area (0.61; 40.0% sensitivity and 94.4% specificity) for differentiating nPDR from healthy eyes.Conclusion: This study showed that analysis of the FAZ based on the ratio of the INL-free zone area to the FAZ area has better accuracy compared to the conventional FAZ area measurement in differentiating eyes with mild to moderate nPDR without any structural abnormalities in the fovea from healthy eyes. [ABSTRACT FROM AUTHOR]

Introduction: Congenital X-linked retinoschisis (XLRS) presents as macular retinoschisis/degeneration in almost all patients and as peripheral retinoschisis in half the patients. Although the optical coherence tomography (OCT) findings of macular retinoschisis have been well investigated, those of peripheral retinoschisis have rarely been reported. This study aimed to report the ultra-widefield OCT findings of the peripheral retina in patients with XLRS., Methods: Medical records of 10 Japanese patients (19 eyes) with clinically and/or genetically diagnosed XLRS were retrospectively reviewed. Funduscopic, electroretinographic, and OCT findings were reviewed and evaluated. Some were also genetically evaluated for the RS1 gene., Results: OCT of the macula revealed schises and/or cystoid changes in the inner nuclear layer (INL) and outer nuclear layer. In contrast, OCT of the peripheral retina revealed schises and/or cystoid changes in the INL in eight eyes (44%), and/or splitting in the ganglion cell layer (GCL) in 10 (56%) of the 18 eyes with clear OCT images. No schisis or cystoid changes were found in the peripheral OCT images of eight eyes (44%). A 16-year-old boy presented with retinal splitting of the GCL and INL of the inferior retina, although he had no ophthalmoscopic peripheral retinoschisis. Genetic examinations were performed on three patients, all of whom had reported missense mutations in the RS1 gene., Conclusion: In XLRS, peripheral bullous retinoschisis results from GCL splitting in the retina. One of the 10 patients with XLRS showed intraretinal retinoschisis in the GCL in the inferior periphery, which was unremarkable on ophthalmoscopy ( occult retinoschisis ). Although both peripheral bullous retinoschisis and occult retinoschisis showed splitting/cystic changes in the GCL, further studies are needed to determine whether occult retinoschisis progresses to bullous retinoschisis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nakajima, Kuniyoshi, Iwahashi, Mano, Hayashi, Kondo, Mizobuchi, Matsushita, Suga, Yoshitake, Nakano, Iwata, Matsumoto and Kusaka.)