Temporal retinal thinning might be an early diagnostic indicator in male pediatric X-linked Alport syndrome.

Anti-glomerular basement membrane (GBM) antibody nephritis is caused by an autoimmune or alloimmune reaction to the NC1 domains of alpha3alpha4alpha5(IV) collagen. Some patients with X-linked Alport syndrome (XLAS) develop post-transplant nephritis mediated by pathogenic anti-GBM alloantibodies to collagen IV chains present in the renal allograft but absent from the tissues of the patient. In this work, the epitopes targeted by alloantibodies from these patients were identified and characterized. All XLAS alloantibodies recognized conformational epitopes in the NC1 domain of alpha5(IV) collagen, which were mapped using chimeric alpha1/alpha5 NC1 domains expressed in mammalian cells. Allograft-eluted alloantibodies mainly targeted two conformational alloepitopes mapping to alpha5NC1 residues 1-45 and 114-168. These regions also encompassed the major epitopes of circulating XLAS alloantibodies, which in some patients additionally targeted alpha5NC1 residues 169-229. Both kidney-eluted and circulating alloantibodies to alpha5NC1 distinctively targeted epitopes accessible in the alpha3alpha4alpha5NC1 hexamers of human GBM, unlike anti-GBM autoantibodies, which targeted sequestered alpha3NC1 epitopes. The results identify two immunodominant alpha5NC1 epitopes as major alloantigenic sites of alpha3alpha4alpha5(IV) collagen specifically implicated in the pathogenesis of post-transplant nephritis in XLAS patients. The contrast between the accessibility of these alloepitopes and the crypticity of autoepitopes indicates that distinct molecular forms of antigen may initiate the immunopathogenic processes in the two forms of anti-GBM disease.

To evaluate macular morphology and function in diabetic macular edema (DME) over the course of intravitreal anti-vascular endothelial growth factor (VEGF) treatment with Ranibizumab. A consecutive series of 39 study eyes with centre-involving DME were included in this study. In all subjects, best-corrected visual acuity (BCVA) according ETDRS protocol, fluorescein angiography (FA), microperimetric macular sensitivity (MP) and Spectral Domain optical coherence tomography (SD-OCT) cross-sectional scans were obtained before treatment and after 3 monthly applied intravitreal Ranibizumab injections. Six different morphological qualities [IS/OS layer integrity, outer nuclear layer (ONL) cysts, ONL cyst size, inner nuclear layer (INL) cysts, blocking phenomenon and subretinal fluid] were graded of each cross-sectional OCT scan before and over the course of treatment by two experienced graders. Correlation analyses between functional and morphological parameters were obtained. Mean BCVA increased from 26 ± 14 to 33 ± 13 letters after 3 consecutive monthly applied Ranibizumab injections (p < 0.001). Central retinal thickness (CRT) decreased from 504 ± 144 to 387 ± 122 μm (p < 0.001). Over the course of treatment, IS/OS continuity improved (index: 0.56 ± 0.52 to 0.43 ± 0.49, Z = -1.415, p = 0.157), ONL cyst prevalence and size decreased significantly (index: 0.61 ± 0.44 to 0.56 ± 0.35, Z = -3.41, p = 0.001 and 1.75 ± 0.88 to 1.17 ± 1.05, Z = -4.02, p < 0.001), INL cyst prevalence decreased (index: 0.35 ± 0.52 to 0.28 ± 0.52, Z = -1.60, p = 0.109), blocking phenomenon did not change significantly (index: 00.12 ± 0.16 to 0.13 ± 0.15, Z = -0.45, p = 0.656) and subretinal fluid almost disappeared (index: 0.10 ± 0.24 vs. 0.00 ± 0.01, Z = -2.56, p = 0.011). Correlation analyses revealed highest significant correlations between ONL cyst prevalence and their size and CRT as well as BCVA and MP before treatment and over the course of treatment. ONL cysts and their size as morphological parameters correlate with retinal function measured with BCVA and microperimetry before and over the course of anti-VEGF therapy with Ranibizumab in patients with DME.

Changes of individual retinal layer thickness post-uneventful cataract surgery determined by spectral-domain optical coherence tomography over a 3-months period

Dear Editor, Mucopolysaccharidosis is an inheritable storage disease with deficiency of lysosomal enzymes that degrade glycosaminoglycans [1]. Mucopolysaccharidosis type II, also known as Hunter syndrome, is an X-linked inherited deficiency of enzyme iduronate 2-sulfatase, resulting in progressive accumulation of dermatan sulfate and heparin sulfate [1]. In many mucopolysaccharidoses, glycosaminoglycans accumulate in the retinal pigment epithelial (RPE) cells, resulting in pronounced lysosomal distension [2]. Previous studies have revealed outer nuclear layer thinning and the absence of outer segments, as well as reduced inner segments from the anterior midperipheral retina [2,3]. However, structural changes of the retina determined by high-resolution spectral domain optical coherence tomography (SD-OCT; Spectralis, Heidelberg Engineering, Heidelberg, Germany) in the early stage of Hunter syndrome with visual impairment have not been reported. With the introduction of SD-OCT, high-resolution images of the retina and optic disc could reveal occult and early structural changes related to disease progression [4]. Herein, we report a patient with Hunter syndrome whose visual acuity decrease was associated with early outer retinal layer changes found on SD-OCT. A 5-year-old boy with Hunter syndrome was referred to our clinic for evaluation of ocular involvement. At initial presentation, his best corrected visual acuities were 20 / 25 in both eyes (OU). Cycloplegic refractive errors were +4.50 Dsph = -3.00 Dcyl × axis 180 in the right eye (OD) and +4.50 Dsph = -3.75 Dcyl × axis 180 in the left eye (OS). Slit lamp biomicroscopy showed clear corneas OU. Funduscopic examination was unremarkable. At the age of 9, he complained of visual acuity decrease OU. On ophthalmic examination, best corrected visual acuities were 20 / 30 OD and 20 / 50 OS. Cycloplegic refractive errors were +4.00 Dsph = -3.50 Dcyl × axis 180 OD and +4.00 Dsph = -4.25 Dcyl × axis 180 OS. Slit lamp biomicroscopy showed clear corneas OU (Fig. 1A and 1B). There was no relative afferent papillary defect. Optic disc margins showed mild blurring. However, lumbar spinal tapping revealed normal intracranial pressure. Visual field testing with Goldmann kinetic perimetry were normal OU. On funduscopic examination, the retina looked grossly intact, but standard electroretinography revealed a reduction of scotopic responses, consistent with rod cell degeneration. Reduced b-wave amplitudes in the maximal responses and reduced oscillatory potentials were also observed OU. Fig. 1 Slit lamp biomicroscopy showed clear corneas in the right (A) and left (B) eyes. (C,D) Comparison of spectral domain optical coherence tomography (SD-OCT; Spectralis, Heidelberg Engineering, Heidelberg, Germany) scans of the macula in early stage Hunter ... SD-OCT showed thickening of the external limiting membrane at the central macula, especially near the fovea (Fig. 1C and 1D). The ellipsoid line formerly known as the inner and outer segment photoreceptor junction appeared normal in thickness and contour, well distinguished from the RPE layer underneath. The peripapillary circular scan images showed a mild increase in bilateral peripapillary retinal nerve fiber layer thickness. Our study demonstrates the structural changes of the retina determined by high-resolution SD-OCT in the early stage of Hunter syndrome. Previously, Yoon et al. [3] reported high-speed, ultrahigh-resolution OCT findings of the retina in Hunter syndrome. Stratus OCT revealed a loss of photoreceptors outside the fovea and cystoid spaces within the inner nuclear layer, ganglion cell layer, and outer nuclear layer [3]. Our patient only showed thickening of the external limiting membrane with no other abnormal findings in the RPE, suggesting that changes of the outer nuclear and photoreceptor layers precede RPE abnormalities. In contrast to our study, the previous case experienced more variable ocular symptoms typical of Hunter syndrome, such as exophthalmos, hypertelorism, and bilateral visual field loss with a ring scotoma pattern, which were not found in our patient. The external limiting membrane, between photoreceptor inner segments and Muller cell apical processes, is filled with the interphotoreceptor matrix, which contains a heterogeneous collection of glycoproteins, enzymes, and glycosaminoglycans [5]. Our SD-OCT findings correlate well with previous histopathological findings in the early stage of Hunter syndrome. The typical histopathological findings reported previously, such as a total loss of RPE, an overall loss of rods and cones, and reduced outer nuclear layer with atrophic bipolar cells, are usually shown as the disease progresses [2]. In conclusion, SD-OCT can be used as a diagnostic modality to monitor patients with Hunter syndrome and to detect subclinical progression of the disease in the early stages.

Purpose: To identify long-term changes in individual retinal layer thickness using automated retinal layer segmentation analysis on high-resolution spectral-domain optical coherence tomography (SD-OCT) scans of eyes with macula-off rhegmatogenous retinal detachment (RRD) treated with vitreoretinal surgery (VRS) and gas or silicone oil tamponade and having single-operation success. Methods: A total of 58 patients operated on by VRS for RRD and followed up for 12 months were imaged by SD-OCT. The patients with retinal diseases such as an epiretinal membrane or cystic macular edema in the operated and fellow eyes were excluded. The thicknesses of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor layer, and retinal pigment epithelium were compared to those of the fellow eyes after the 12-month follow-up. Thickness changes in individual layers were quantitatively analyzed in the operated and fellow eyes and correlated with the type of tamponade used in the surgery. Results: Spectralis OCT automated segmentation software was used for the retinal layer analysis. There were 22 females and 36 males. Their mean age was 60.7 ± 11.2 years. The mean central macular thickness was 214.3 ± 29.5 µm in the operated and 229.7 ± 21.7 µm in the fellow eyes (p = 0.008). There was a statistically significant difference between the operated and the healthy fellow eyes in the following layers: the RNFL (p = 0.017), GCL (p = 0.02), INL (p = 0.005), and ONL (p = 0.008) in the central foveal area; the RNFL (p < 0.001), INL (p = 0.017), and ONL (p = 0.022) in the perifoveal ring; and the RNFL (p < 0.001), IPL (p = 0.042), INL (p = 0.001), and OPL (p = 0.001) in the peripheral ring. The logMAR best corrected visual acuities were 2.51 ± 0.68 and 2.69 ± 0.62 at baseline and 0.60 ± 0.38 and 0.50 ± 0.38 at month 12 in the silicone oil tamponade (n = 28) and the gas tamponade (n = 30) group (p = 0.52 and p = 0.21, respectively). The foveal GCL, OPL, and ONL and the perifoveal GCL and IPL were statistically significantly thinner in the silicone oil tamponade group (p = 0.01, p = 0.046, p = 0.024, p = 0.006, and p = 0.011, respectively). Conclusions: Significant changes were observed in the retinal layers after VRS for RRD. Individual retinal layers seem to be affected 1 year after VRS for RRD. The type of tamponade can influence the thickness of the retinal layers. The thickness of the retinal layers was significantly preserved in eyes treated with gas tamponade when compared to those treated with silicone oil tamponade in the long term. Further studies are needed to validate our results.

We evaluated layer-by-layer retinal thickness in spectral-domain optical coherence tomography (SD-OCT), determined by automated segmentation analysis (ASA) software in healthy and early age-related maculopathy (ARM) eyes. There were 57 eyes (specifically, 19 healthy eyes under 60 years old, 19 healthy eyes over 60, and 19 ARM eyes) recruited into this cross-sectional study. The mean ages were 36.78 (SD, ±13.82), 69.89 (SD, ±6.14), and 66.10 (SD, ±8.67) years, respectively, in the three study groups. The SD-OCT scans were transferred into a dedicated software program that performed automated segmentation of different retinal layers. Automated layer segmentation showed clear boundaries between the following layers: retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCL+IPL), inner nuclear layer plus outer plexiform layer (INL+OPL), outer nuclear layer (ONL), and RPE complex. The thickness of the RNFL, ONL, and RPE layers did not show a statistically significant change across the three groups by ANOVA (P = 0.10, P = 0.09, P = 0.15, respectively). The thickness of GCL+IPL and INL+OPL was significantly different across the groups (P < 0.01), being reduced in the ARM eyes compared to healthy eyes, under and over 60 years old. The early morphologic involvement of the GCL+IPL and INL+OPL layers in ARM eyes, as revealed by the ASA, could be related to early anatomic changes described in the inner retina of ARM eyes. This finding may represent a morphologic correlation to the deficits in postreceptoral retinal function in ARM eyes.

Objective: We used ultra-high resolution spectral domain optical coherence tomography (UHR-OCT) to analyze the subclinical changes in retinal neurons, axon injury, and retinal thickness in neuromyelitis optica spectrum disorders (NMOSD) patients. Methods: This case-control study included 21 cases of NMOSD patients and 20 matched healthy volunteers (control group). The NMOSD patients were divided into a subgroup without optic neuritis (NO-ON) (13 eyes) and a subgroup with optic neuritis (ON) group (13 eyes). The thickness of the total retina of each patient and control subject was evaluated by using UHR-OCT. Data of each layer were analyzed using one-way ANOVA. Results: Except at the central region, the total retinal thickness of the ON group in whole mapping images was significantly thinner than the control group and NO-ON group. There were significant differences in total thickness between the NO-ON group and the control group in some regions (nasal interior [NI], P=0.011; temporal interior[TI], P=0.003; superior exterior [SE], P=0.019; inferior exterior [IE], P=0.002). The thicknesses of the retinal nerve fiber layer (RNFL) and the combined ganglion cell layer and inner plexiform layer (GCL+IPL) in the ON group was significantly thinner in each quadrant compared with the control group (P < 0.001). The RNFL thickness of the NO-ON group was thinner in the nasal and temporal areas compared with the control group (NI, P=0.049; TI and temporal exterior [TE], P < 0.001). The GCL+IPL thickness in the NO-ON group was thinner than control group (SE, P < 0.001; IE, P=0.002). The thickness of inner nuclear layer (INL) in the ON group was thicker than in the control group (superior interior [SI], P=0.001; inferior interior [II], P=0.003; TE, P=0.043); however the thickness of the INL in the NO-ON group was thinner than in the control group (SE, P=0.015; IE, P=0.012). The thickness of Henle fiber layer and outer nuclear layer (HFL+ONL) in the NO-ON group was thinner than for the control group (SI, P=0.009; SE, P=0.018; II, P=0.001; IE, P=0.001 ), but there were no significant differences between the ON group and the control group. Conclusions: There were significant changes in the different retinal layers of NMOSD patients compared to healthy controls. The thicknesses of RNFL and GCIPL in the NO-ON subgroup were decreased, suggesting that NMOSD patients with no optic neuritis potentially have structural damage in the retinal nerve. Key words: neuromyelitis optica spectrum disorders; optical coherence tomography; neuro damage; aquaporin-4

X-linked Alport syndrome (XLAS), caused by mutations in the COL4A5 gene, is an X-linked hereditary disease typically characterized by renal failure, hearing loss, and ocular abnormalities. It is a leading hereditary cause of end-stage renal disease (ESRD) worldwide. Studies on the genotype-phenotype correlation in Alport syndrome suggest that splicing mutations result in more severe clinical phenotypes than missense mutations. Determining whether COL4A5 mutations lead to aberrant mRNA splicing is critical for diagnosis and prognosis. This study retrospectively reviewed pediatric XLAS patients with COL4A5 gene mutations from a single-center cohort, summarizing and analyzing their clinical features. Minigene assay was employed to evaluate the mRNA splicing functionality of 26 single-nucleotide variants (SNVs), both intronic and exonic, identified in XLAS patients. Bioinformatics tools were used to evaluate the accuracy and sensitivity of splicing mutation prediction. Additionally, linear mixed models were applied to analyze the relationship between mutation types and prognosis in patients' estimated glomerular filtration rate (eGFR), exploring genotype-phenotype correlations. In this cohort, we screened 41 XLAS pediatric patients, including 32 with confirmed XLAS and nine suspected XLAS. The cohort included 21 males (51.2%) and 20 females (48.8%), with a median age at onset of 4.42 years. Among the patients, 22 presented with both hematuria and proteinuria, while 18 exhibited hematuria alone. Notably, only one patient had isolated proteinuria. Regarding mRNA splicing, among the 26 intronic and exonic SNVs, 10 mutations (38.5%) were found to cause aberrant mRNA splicing, as demonstrated by the minigene assay. Sensitivity and specificity assessments of bioinformatics tools revealed that ESE Finder demonstrated higher sensitivity, while RNA Splicer exhibited greater specificity. Furthermore, These splicing abnormalities were closely associated with a faster decline in eGFR. This study demonstrates that 38.5% of SNVs in the COL4A5 gene result in aberrant mRNA splicing, which is closely linked to renal function decline in XLAS. Splicing mutations are correlated with more rapid renal progression, highlighting the importance of determining the splicing effects of SNVs during genetic screening for XLAS.

X-linked Alport syndrome (XLAS) is a progressive hereditary kidney disease caused by mutations in the COL4A5 gene encoding the type IV collagen α5 chain. To date, 11 cases having somatic mosaic variants in COL4A5 have been reported; however, all of them involved single-nucleotide variations (SNVs). Here, we report a female XLAS patient with somatic mosaicism identified by copy number variation (CNV) in COL4A5. The case was a 35-year-old female, the mother of the proband, whose only clinical symptom was hematuria. The proband, who was the son of this patient, was diagnosed with XLAS by gene testing, which showed a large hemizygous deletion from exon 3-51 in COL4A5 detected by next-generation sequencing and then confirmed by multiplex ligation-dependent probe amplification (MLPA). Then, MLPA analysis revealed that the female patient had the same deletion with only a 20% copy number reduction compared with a normal female control; she was thus diagnosed with XLAS with somatic mosaicism. CNVs in COL4A5 are relatively rare and, to the best of our knowledge, somatic mosaic variants with CNVs have never been reported. This case clearly featured a germline variant because the patient's son exhibited XLAS. This is thus the first case report on an XLAS patient having CNV in COL4A5 with somatic mosaicism. The obtained findings were very important for the genetic counseling of this family.

X-linked Alport syndrome (XLAS) caused by X-linked COL4A5 gene mutation is a hereditary disease that affects mainly the kidney. XLAS patients, especially males whose single copy of the COL4A5 gene is disrupted, suffer from a life-threatening renal disease, the mechanism of which remains unclear. Renal fibrosis is a characteristic pathology observed in XLAS kidney tissue. However, the molecular path from COL4A5 loss-of-function to fibrotic pathology is largely unknown. On the basis of a previously established XLAS mouse model, our study revealed an activated CD44-TGFβ signaling known to strongly promote fibrosis, along with an increased level of low molecular weight hyaluronan (LMW-HA) instead of high molecular weight hyaluronan (HMW-HA), to activate CD44-dependent TGFβ signaling in XLAS renal tissues. Additionally, hyaluronan synthase 2 (HAS2), an enzyme primarily responsible for HA production, was found to be upregulated in XLAS. In particular, in vitro studies revealed that COL4A5 knockdown in human kidney-derived HEK-293 cells can upregulate HAS2 at both the RNA and protein levels. The novel contribution of our study is finding that COL4A5 deficiency may lead to HAS2 overexpression and HA accumulation to activate CD44-TGFβ signaling, thereby promoting fibrosis, possibly suggesting that HAS2 and CD44 are potential therapeutic targets for impeding renal fibrosis in XLAS.

Purpose: The aim of our study is to investigate the effects of hyperbaric oxygen (HBO2) therapy on retinal layers in healthy eyes. Method: Thirty patients who were taken to outpatient HBO2 for any indication were included in the study. All patients underwent 10 sessions of HBO2; 20 healthy patients were taken as the control group. We used the spectral-domain optical coherence tomography (SD-OCT) to obtain automated measurements of thickness for each retinal layer – i.e., the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) and retinal pigment epithelium (RPE) – and to conduct foveal (central 1 mm), inner-ring (parafoveal 1 to 3mm), and outer-ring (perifoveal 3 to 6mm) retinal layer measurements. Retinal OCT scans were performed before HBO2, after the first and 10th sessions. All retinal layer thicknesses were assessed with SD-OCT software system and compared between each visit. Retinal thicknesses were calculated in the central, inner ring and outer ring subfields (nine quadrants). Results: In SD-OCT measurements, there were no statistically significant difference before HBO2, after the first and 10th sessions in terms of foveal, inner-ring and outer-ring thickness of RNFL, GCL, IPL, INL, OPL, ONL and RPE. Conclusions: Our study demonstrated that there was no change in the thickness of the retinal layers after the first and 10th sessions in healthy eyes.

ABSTRACTBackground and objectives: Alport syndrome is an inherited disease characterized by renal failure, hearing loss, and ocular abnormalities, including temporal retinal thinning. This study compared retinal thinning in Alport syndrome and other renal diseases.Methods: Alport syndrome was diagnosed on renal biopsy and genetic testing. Subjects underwent optical coherence tomography (OCT) (Spectralis OCT, Heidelberg Instruments). Retinal thinning was determined from horizontal macular OCT scans through the foveal center using the formula: Temporal thickness index (TTI) = (nasal – temporal thickness) ÷ nasal thickness × 100%, and compared with the normal range for each age group. Statistical analysis was performed using Student’s t test, Mann–Whitney U test, and ROC analysis (SPPS, IBM).Results: The mean temporal retinal thickness index was 12.4 ± 5.2% in men (n = 19) and 7.4 ± 1.4% in women (n = 28) with X-linked Alport syndrome; 13.1 ± 4.5% (n = 4) in recessive disease; 6.4 ± 2.2% (n = 5) in Thin basement membrane nephropathy; and 6.3 ± 3.3% (n = 14) in other renal diseases. Thinning was worse in men than women with X-linked disease (p < 0.01), and worse in men who developed early onset renal failure (R2 = 0.75). Temporal retinal thinning was 84% sensitive for men with X-linked Alport syndrome and 67% specific (AUC = 0.83) compared with other renal diseases.Conclusions: Retinal temporal thinning is diagnostic for X-linked Alport syndrome in men and distinguishes them this condition from Thin basement membrane nephropathy, but only in men (p = 0.002). Temporal retinal thinning may also identify men and women with the rarer autosomal recessive disease.

Background/aimsTo compare the thickness of each retinal layer of amblyopic and fellow eyes in patients with unilateral amblyopia.MethodsHorizontal and vertical spectral-domain optical coherence tomography scans through the fovea were obtained...

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.

To determine the total alpha-synuclein (αSyn) reflex tears and its association with retinal layers thickness in Parkinson's disease (PD). Fifty-two eyes of 26 PD subjects and 52 eyes of age-and sex-matched healthy controls were included. Total αSyn in reflex tears was quantified using a human total αSyn enzyme-linked immunosorbent assay (ELISA) kit. The retinal thickness was evaluated with spectral-domain optical coherence tomography. The Movement Disorder Society-Unified Parkinsońs Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS), and Montreal Cognitive Assessment (MoCA) were used to assess motor, non-motor, and cognition. In PD, total αSyn levels were increased compared to control subjects [1.76pg/mL (IQR 1.74-1.80) vs 1.73pg/mL (IQR 1.70-1.77), p < 0.004]. The nerve fiber layer, ganglion cell layer, internal plexiform layer, inner nuclear layer, and outer nuclear layer were thinner in PD in comparison with controls (p < 0.05). The outer plexiform layer and retinal pigment epithelium were thicker in PD (p < 0.05). The total αSyn levels positively correlated with the central volume of the inner nuclear layer (r = 0.357, p = 0.009). Total αSyn reflex tear levels were increased in subjects with PD compared to controls. PD patients showed significant thinning of the inner retinal layers and thickening of outer retinal layers in comparison with controls. Total αSyn levels positively correlate with the central volume of the inner nuclear layer in PD. The combination of these biomarkers might have a possible role as a diagnostic tool in PD subjects.