Photoreceptor Layer Thickness Research Articles

Analysing early changes of photoreceptor layer thickness following surgery in eyes with epiretinal membranes.

To analyse short-term changes of mean photoreceptor thickness (PRT) on the ETDRS-grid after vitrectomy and membrane peeling in patients with epiretinal membrane (ERM). Forty-eight patients with idiopathic ERM were included in this prospective study. Study examinations comprised best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) before surgery, 1 week (W1), 1 month (M1) and 3 months (M3) after surgery. Mean PRT was assessed using an automated algorithm and correlated with BCVA and central retinal thickness (CRT). Regarding PRT changes of the study eye in comparison to baseline values, a significant decrease at W1 in the 1 mm, 3 mm and 6 mm area (all p-values < 0.001), at M1 (p = 0.009) and M3 (p = 0.019) in the central 1 mm area, a significant increase at M3 in the 6 mm area (p < 0.001), but no significant change at M1 in the 3 mm and 6 mm area and M3 in the 3 mm area (all p-values > 0.05) were observed. BCVA increased significantly from baseline to M3 (0.3LogMAR-0.15LogMAR, Snellen equivalent = 20/40-20/28 respectively; p < 0.001). There was no correlation between baseline PRT and BCVA at any visit after surgery, nor between PRT and BCVA at any visit (all p-values > 0.05). Decrease in PRT in the 1 mm (p < 0.001), 3 mm (p = 0.013) and 6 mm (p = 0.034) area after one week correlated with the increase in CRT (449.9 µm-462.2 µm). Although the photoreceptor layer is morphologically affected by ERMs and after their surgical removal, it is not correlated to BCVA. Thus, patients with photoreceptor layer alterations due to ERM may still benefit from surgery and achieve good functional rehabilitation thereafter.

Associations Between HbA1c Across the Normal Range, Diagnosed, and Undiagnosed Diabetes and Retinal Layer Thickness in UK Biobank Cohort.

The purpose of this study was to investigate the association between glycated hemoglobin (HbA1c) levels and retinal sub-layer thicknesses in people with and without diabetes. We included 41,453 UK Biobank participants aged 40 to 69 years old. Diabetes status was defined by self-report of diagnosis or use of insulin. Participants were categorized into groups: (1) those with HbA1c <48 mmol/mol were subdivided into quintiles according to normal range of HbA1c; (2) those previously diagnosed with diabetes with no evidence of diabetic retinopathy; and (3) undiagnosed diabetes: >48 mmol/mol. Total macular and retinal sub-layer thicknesses were derived from spectral-domain optical coherence tomography (SD-OCT) images. Multivariable linear regression was used to evaluate the associations between diabetes status and retinal layer thickness. Compared with participants in the second quintile of the normal HbA1c range, those in the fifth quintile had a thinner photoreceptor layer thickness (-0.33 µm, P = 0.006). Participants with diagnosed diabetes had a thinner macular retinal nerve fiber layer (mRNFL; -0.58 µm, P < 0.001), photoreceptor layer thickness (-0.94 µm, P < 0.001), and total macular thickness (-1.61 µm, P < 0.001), whereas undiagnosed diabetes participants had a reduced photoreceptor layer thickness (-1.22 µm, P = 0.009) and total macular thickness (-2.26 µm, P = 0.005). Compared to participants without diabetes, those with diabetes had a thinner mRNFL (-0.50 µm, P < 0.001), photoreceptor layer thickness (-0.77 µm, P < 0.001), and total macular thickness (-1.36 µm, P < 0.001). Participants with higher HbA1c in the normal range had marginally thinner photoreceptor thickness, whereas those with diabetes (including undiagnosed diabetes) had meaningfully thinner retinal sublayer and total macular thickness. We showed that early retinal neurodegeneration occurs in people whose HbA1c levels are below the current diabetes diagnostic threshold; this might impact the management of pre-diabetes individuals.

Retinal photoreceptor layer thickness has disease specificity and distinguishes predicted FTLD-Tau from biomarker-determined Alzheimer's disease

While Alzheimer's disease (AD) is associated with inner retina thinning (retinal nerve fiber layer and ganglion cell layer), we have observed photoreceptor outer nuclear layer (ONL) thinning in patients with frontotemporal lobar degeneration tauopathy (FTLD-Tau) compared to normal controls. We hypothesized that ONL thinning may distinguish FTLD-Tau from patients with biomarker evidence of AD neuropathologic change (ADNC) and will correlate with FTLD-Tau disease severity.Predicted FTLD-Tau (pFTLD-Tau; n = 21; 33 eyes) and predicted ADNC (pADNC; n = 24; 46 eyes) patients were consecutively enrolled, underwent optical coherence tomography macula imaging, and disease was categorized (pFTLD-Tau vs. pADNC) with cerebrospinal fluid biomarkers, genetic testing, and autopsy data when available. Adjusting for age, sex, and race, pFTLD-Tau patients had a thinner ONL compared to pADNC, while retinal nerve fiber layer and ganglion cell layer were not significantly different. Reduced ONL thickness correlated with worse performance on Folstein Mini-Mental State Examination and clinical dementia rating plus frontotemporal dementia sum of boxes for pFTLD-Tau but not pADNC. Photoreceptor ONL thickness may serve as an important noninvasive diagnostic marker that distinguishes FTLD-Tau from AD neuropathologic change.

Microglia Preserve Visual Function in a Mouse Model of Retinitis Pigmentosa with Rhodopsin-P23H Mutant.

Most forms of outer retinal degenerative diseases involve the ectopic accumulation of microglia/macrophages in the subretinal space, including retinitis pigmentosa. However, their role in the loss of photoreceptor function during retinal degeneration remains unknown. Here, we examined the effect of conditional microglial depletion on photoreceptor numbers and visual function in mice with the rhodopsin P23H mutation, a dominant form of retinitis pigmentosa in humans. We found that microglial depletion led to an elevated level of rhodopsin and increased photoreceptor layer thickness. However, overall electrophysiological functions of the retina were reduced with microglial depletion. Therefore, these results identify an essential role of microglia specially in preserving visual function in outer retinal degeneration.

Multimodal visual system analysis as a biomarker of visual hallucinations in Parkinson's disease.

Visual hallucinations (VH) are present in up to 75% of Parkinson's disease (PD) patients. However, their neural bases and participation of the visual system in VH are not well-understood in PD. Seventy-four participants, 12 PD with VH (PDVH), 35 PD without VH (PDnoVH) and 27 controls underwent a battery of primary visual function and visual cognition tests, retinal optical coherence tomography and structural and resting-state functional brain MRI. We quantified cortical thickness with Freesurfer and functional connectivity (FC) of Visual (VIS), Fronto-Parietal (FP), Ventral Attention (VAN) and Dorsal Attention (DAN) networks with CONN toolbox. Group comparisons were performed with MANCOVA. Area Under the Curve (AUC) was computed to assess the ability of visual variables to differentiate PDVH and PDnoVH. There were no significant PDVH vs PDnoVH differences in disease duration, motor manifestations, general cognition or dopamine agonist therapy (DA) use. Compared to PDnoVH and HC, and regardless of DA use, PDVH showed significantly reduced contrast sensitivity, visuoperceptive and visuospatial abilities, increased retina photoreceptor layer thickness, reduced cortical thickness mostly in right visual associative areas, decreased between-network VIS-VAN and VAN-DAN connectivity and increased within-network DAN connectivity. The combination of clinical and imaging variables that best discriminated PDVH and PDnoVH (highest AUC), where within-network DAN FC, photoreceptor layer thickness and cube analysis test from Visual Object and Space Perception Battery (accuracy of 81.8%). Compared to PDnoVH, PDVH have specific functional and structural abnormalities within the visual system, which can be quantified non-invasively and could potentially constitute biomarkers for VH in PD.

MACULAR MICROVASCULATURE IN X-LINKED RETINOSCHISIS: Optical Coherence Tomography and Optical Coherence Tomography Angiography Study.

The study aimed to evaluate the macular microvasculature of X-linked retinoschisis (XLRS) and identify correlations between vascular changes, structural changes, and functional outcome. Genetically confirmed XLRS patients and heathy control subjects underwent complete ophthalmic examination, dilated funduscopic examination, optical coherence tomography, and optical coherence tomography angiography. Schisis distribution, outer plexiform layer discontinuation, photoreceptor layer thickness, and photoreceptor outer segment length were reviewed using optical coherence tomography. Vascular flow density and foveal thickness at foveal and parafoveal area were measured using optical coherence tomography angiography. A total of 17 eyes of 9 XLRS patients and 22 eyes of 11 control subjects were examined from July 2018 to August 2020. Flow density in the deep capillary plexus at foveal and parafoveal area decreased in XLRS patients compared with control subjects (P = 0.014 and 0.001, respectively), whereas foveal avascular zone area and perimeter remarkably increased (P = 0.015 and 0.001, respectively). Although outer and total retinal layers were significantly thicker in XLRS, inner retinal layer was thinner with reduced photoreceptor layer thickness and shortened photoreceptor outer segment length (P < 0.001 and P < 0.001, respectively). Foveal flow loss in deep capillary plexus, foveal avascular zone enlargement, thinner inner retina and photoreceptor layer thickness, and shortened photoreceptor outer segment length correlated with best-corrected visual acuity. X-linked retinoschisis eyes exhibit decreased flow density in the deep capillary plexus and variable foveal avascular zone with enlarged perimeter. Structural deterioration of the photoreceptor best reflects the degenerative changes, whereas microvascular alteration shows considerable correlation with functional outcome in XLRS.

Predicting Topographic Disease Progression and Treatment Response of Pegcetacoplan in Geographic Atrophy Quantified by Deep Learning

To identify disease activity and effects of intravitreal pegcetacoplan treatment on the topographic progression of geographic atrophy (GA) secondary to age-related macular degeneration quantified in spectral-domain OCT (SD-OCT) by automated deep learning assessment. Retrospective analysis of a phase II clinical trial study evaluating pegcetacoplan in GA patients (FILLY, NCT02503332). SD-OCT scans of 57 eyes with monthly treatment, 46 eyes with every-other-month (EOM) treatment, and 53 eyes with sham injection from baseline and 12-month follow-ups were included, in a total of 312 scans. Retinal pigment epithelium loss, photoreceptor (PR) integrity, and hyperreflective foci (HRF) were automatically segmented using validated deep learning algorithms. Local progression rate (LPR) was determined from a growth model measuring the local expansion of GA margins between baseline and 1 year. For each individual margin point, the eccentricity to the foveal center, the progression direction, mean PR thickness, and HRF concentration in the junctional zone were computed. Mean LPR in disease activity and treatment effect conditioned on these properties were estimated by spatial generalized additive mixed-effect models. LPR of GA, PR thickness, and HRF concentration in μm. A total of 31,527 local GA margin locations were analyzed. LPR was higher for areas with low eccentricity to the fovea, thinner PR layer thickness, or higher HRF concentration in the GA junctional zone. When controlling for topographic and structural risk factors, we report on average a significantly lower LPR by -28.0% (95% confidence interval [CI], -42.8 to -9.4; P = 0.0051) and -23.9% (95% CI, -40.2 to -3.0; P = 0.027) for monthly and EOM-treated eyes, respectively, compared with sham. Assessing GA progression on a topographic level is essential to capture the pathognomonic heterogeneity in individual lesion growth and therapeutic response. Pegcetacoplan-treated eyes showed a significantly slower GA lesion progression rate compared with sham, and an even slower growth rate toward the fovea. This study may help to identify patient cohorts with faster progressing lesions, in which pegcetacoplan treatment would be particularly beneficial. Automated artificial intelligence-based tools will provide reliable guidance for the management of GA in clinical practice.

Effect of aging and lifestyle on healthy macular photoreceptors and retinal pigment epithelium-Bruch membrane complex thickness.

Investigate how aging and some lifestyle factors correlate with changes in macular photoreceptor and retinal pigment epithelium-Bruch membrane complex layers thickness in a sample of healthy population by using OCT segmentation technique. A cross-sectional study conducted at the ophthalmology department in the Medical City in Baghdad. All participants underwent an interview of medical history and lifestyle habits. Maculae of all participants were scanned using spectral domain optical coherence tomography, followed by manual segmentation of retinal layers. The study included 152 healthy participants (152 eyes), their mean age was 57.3 ± 6.7 years, gender distribution was 82(53.9%) males and 70(46.1%) females. There was a decrement in retinal pigment epithelium-Bruch membrane layer thickness at central subfield (500 µm radius from fovea minimum) by - 0.178 µm/year (p = 0.019), inner macula (500-1500 µm radius from fovea minimum) by - 0.263 µm/year (p = 0.002), outer macula (1500-3000 µm radius from fovea minimum) by - 0.225 µm/year (p = 0.015) with no statistically significant effect on photoreceptor thickness. Physical activity and smoking had statistically no significant effect on these layers thickness, however smokers had higher photoreceptor thickness at fovea minimum and central subfield. Body mass index increase by one kg/m2 correlated with a decrement in photoreceptor layer thickness by - 0.108 µm (p = 0.007). Aging process affected the retinal pigment epithelium-Bruch membrane complex and photoreceptor layer thickness in a healthy population, and this process can be slowed down by avoiding some lifestyles which aggravate these changes like obesity.

Genetic, environmental and other risk factors for progression of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a commonly inherited disease of the retina, which is characterized by progressive loss of visual function due to specific genetic mutations. There are many risk factors that may have effect on the progression of RP, such as inheritance patterns, genotype, gender, age, smoking, physical activity, and other demographic and environmental factors. Baseline visual field conditions, changes of ellipsoid zone, photoreceptor layer thickness, and choroidal structure are reported to be the phenotype risk factors for RP progression. Moreover, aqueous flare and high-sensitivity C-reactive protein are probable inflammation biomarkers for assessing the progression of RP. Increased oxidative stress is considered to be one of the potential factors for the existence of RP. The risk factors can be combined to form a corresponding prediction model to predict disease progression. This review is to summarize the current literature that studies the genetic, environmental, phenotypic, demographic, inflammatory and other risk factors of RP progression and discuss the most reliable risk factors that could provide predictive models.

Comparison of Each Retinal Layer Thicknesses between Eyes with Central Retinal Vein Occlusion and Normal Contralateral Eyes.

PurposeTo evaluate the difference in each retinal layer thickness in central retinal vein occlusion (CRVO) with resolved macular edema after intravitreal antivascular endothelial growth factor injection and normal contralateral eyes..MethodsPatients with ischemic and nonischemic CRVO whose macular edema resolved after intravitreal antivascular endothelial growth factor injections and did not recur for at least 6 months, and a normal contralateral eye were enrolled. Each retinal layer thickness between CRVO and normal contralateral eyes was compared according to Early Treatment Diabetic Retinopathy Study subfields using spectral domain optical coherence tomography.ResultsThe thicknesses of outer nuclear layer, photoreceptor layer, and retinal pigment epithelium in central ring, ganglion cell layer, inner plexiform layer, outer nuclear layer, and photoreceptor layer in the inner ring, and ganglion cell layer in the outer ring of CRVO eyes were significantly thinner than those of normal contralateral eyes (all p < 0.05). Whereas, inner nuclear layer and outer plexiform layer thicknesses in central ring of CRVO eyes were 23.86 ± 8.8 and 25.76 ± 7.6 μm, respectively, which was significantly thicker than those of normal contralateral eyes (19.52 ± 7.7 and 22.76 ± 6.5 μm; p = 0.019 and p = 0.043, respectively). Additionally, the mean best-corrected visual acuity of CRVO eyes were significantly correlated with photoreceptor layer thickness in central ring (p = 0.005).ConclusionsIn CRVO eyes with resolved macular edema, the outer retinal layers were thinner as well as inner retinal layers, whereas inner plexiform layer and outer nuclear layer were thicker than normal fellow eyes. Additionally, photoreceptor layer thickness in foveal area had a significant impact on visual acuity in CRVO.

Enhanced cGMP Interactor Rap Guanine Exchange Factor 4 (EPAC2) Expression and Activity in Degenerating Photoreceptors: A Neuroprotective Response?

The disease retinitis pigmentosa (RP) leads to photoreceptor degeneration by a yet undefined mechanism(s). In several RP mouse models (i.e., rd mice), a high cyclic GMP (cGMP) level within photoreceptors is detected, suggesting that cGMP plays a role in degeneration. The rap guanine exchange factor 4 (EPAC2) is activated by cyclic AMP (cAMP) and is an accepted cGMP-interacting protein. It is unclear whether and how cGMP interacts with EPAC2 in degenerating photoreceptors; we therefore investigated EPAC2 expression and interactions with cGMP and cAMP in retinas of the rd1 and rd10 models for retinal degeneration. EPAC2 expression in the photoreceptor layer increased significantly during rd1 and rd10 degeneration, and an increase in EPAC2 interactions with cGMP but not cAMP in the rd1 was also seen via a proximity ligation assay on histological sections. Retinal explant cultures revealed that pharmacological inhibition of the EPAC2 activity reduced the photoreceptor layer thickness in the rd10 retina, suggesting that EPAC2 inhibition promotes degeneration. Taken together, our results support the hypothesis that high degeneration-related cGMP leads to increased EPAC2 and cGMP interactions, inhibiting EPAC2. By inference, EPAC2 could have neuroprotective capacities that may be exploited in the future.

Comparison of the qualitative and quantitative optical coherence tomographic features between sudden acquired retinal degeneration syndrome and normal eyes in dogs.

To quantitatively and qualitatively characterize the retinal optical coherence tomographic features of sudden acquired retinal degeneration syndrome (SARDS) and SARDS suspect dogs. Fourteen SARDS affected dogs, 11 age-, breed-, and sex-matched control dogs, and two SARDS suspect dogs. Spectral-domain optical coherence tomography (OCT) images were used to evaluate the quantitative features, including thickness, intereye asymmetry, and longitudinal changes in retinal layer thickness and the qualitative features, including retinal architecture and vitreous haze. Mean outer retinal layer thickness (ORT), outer nuclear layer thickness (ONL), and photoreceptor layer thickness (PRL) were significantly lower in the SARDS group, whereas mean inner retinal layer thickness was significantly higher in the SARDS group than in the control group. While thickness values of all retinal layers did not differ significantly between paired eyes in each group, the absolute intereye asymmetries in the ORT (p<.0001), ONL (p=.008), and PRL (p<.0001) were significantly higher in the SARDS group than in the control group. Some SARDS patients and SARDS suspects had a greater PRL than the control group, and serial OCT evaluation showed an increase in PRL in one SARDS suspect. Vitreous haze severity was greater in the SARDS group than in the control group (vitreous relative intensity, p=.030). We described the OCT features of SARDS patients and suspects. In particular, PRL thickening in the SARDS suspects might indicate an early change in SARDS. Although further studies are needed, this finding might provide new insights into the pathogenesis of SARDS.

The Relationship Between Choroidal and Photoreceptor Layer Thickness With Visual Acuity in Highly Myopic Eyes.

PurposeThe aim of this study was to evaluate the choroidal and photoreceptor thickness in highly myopic eyes and its correlation with visual acuity.MethodsThis is a cross-sectional, observational study involving 57 eyes of 57 highly myopic subjects [spherical equivalent ≥ –6 diopters (D) or axial length ≥ 26 mm] seen in a tertiary institutional center. Eyes with any clinical evidence of maculopathy or amblyopia were excluded. All subjects underwent a refraction assessment, visual acuity, axial length measurement using the IOL Master, and full ocular assessment. Eyes were imaged using Spectralis Optical Coherence Tomography by one experienced operator. Two independent investigators manually measured subfoveal choroidal thickness (SFCT) and foveal photoreceptor thickness (FPT).ResultsThe mean SFCT was 195.88 ± 87.63 μm (range: 32–373) and mean FPT was 96.68 ± 11.23 μm (range: 67–100), after correction for ocular magnification. The best corrected visual acuity (BCVA) in LogMAR was negatively correlated with SFCT (r = –0.510, p = 0.001) and FPT (r = –0.397, p = 0.002) and positively correlated with age (r = 0.418, p = 0.001) and axial length (r = 0.551, p = 0.001). Multiple linear regression analysis showed that age, axial length, and corrected FPT were significant risk factors for poorer BCVA (p = 0.021, < 0.001, and 0.02, respectively).ConclusionFPT, age, and axial length are significant moderate predictive factors for poorer visual acuity in highly myopic eyes without myopic maculopathy. Thinner SFCT does not translate into poorer vision.

Retinal Degeneration in Patients with Wilson's Disease: An OCT Study in Asian Indian Population.

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. We aimed to study the abnormalities in the retinal layers in patients with WD using optical coherence tomography (OCT). The study is a chart review of 16 patients with WD (six females) who underwent OCT at our hospital during follow-up visits. Spectral-domain OCT was performed in all subjects to assess the thickness of macula and retinal nerve fiber layer (RNFL) and the data was compared with 14 healthy controls (three females). The mean age of the patients was 20.81 ± 7.47 years and controls was 26.86 ± 9.95 years. The mean age at the onset of the illness was 16.25 ± 5.57 years (range 11-28 years) with the mean duration of illness being 4.81 ± 3.31 years at the final follow-up examination. The mean macular thickness was found to be significantly reduced in patients (232.13 ± 19.39) when compared to controls (271.30 ± 17.32 μm; P = 0.01). There was a significant difference in the ganglion cell and inner plexiform (GCIP) layer between the patients (86.83 ± 8.20 μm) and controls (97.72 ± 5.31 μm; P = 0.01). In addition, the outer nuclear layer with the photoreceptor layer (ONL + PRL) thickness was also reduced in WD (93.90 ± 10.23 μm vs. 108.43 ± 10.00 μm; P = 0.01) There was no change in the RNFL thickness, between the two groups (P = 0.53). Abnormalities of the retinal layers were observed in the patients with WD. OCT is a non-invasive tool to identify and quantify the abnormalities of the retinal layers.

Predictors of visual recovery in patients with macular edema secondary to central retinal vein occlusion after treatment with Conbercept

BackgroundThe use of Spectral domain optical coherence tomography (SD-OCT) to evaluate the predictors of visual acuity-recovery in patients treated with conbercept for macular edema (ME) secondary to central retinal vein occlusion (CRVO) has rarely been seen. We collected 26 CRVO-ME patients with different OCT measures at 6 months follow-up to identify the factors that are most strongly correlated with the best-corrected visual acuity (BCVA) post-treatment in CRVO-ME patients treated with conbercept.PurposeTo evaluate the effectiveness of intravitreal conbercept injections for the treatment of CRVO-ME and to determine the major predictors of best-corrected visual acuity (BCVA) post-treatment.MethodsA retrospective study methodology was used. Twenty-six eyes from 26 patients with CRVO-ME were enrolled in the study. After an initial intravitreal injection of conbercept (0.5 mg/0.05 ml), monthly injections for up to 6 months were given following a 1 + PRN (pro re nata) regimen. Data collected at monthly intervals included measurements of the logMAR BCVA, central subfield thickness (CST), macular volume (MV), photoreceptor layer thickness (PLT), outer nuclear layer thickness (ONLT), and the disrupted ellipsoid zone (DEZ). The correlation between BCVA, before and after injections, and each of CST, MV, PLT, ONLT, DEZ was analyzed.ResultsThe logMAR BCVA in months 3 and 6 post-injection was significantly improved relative to the baseline. In this same period the CST, MV, PLT, ONLT and DEZ were also significantly improved relative to the baseline. There was a negative correlation between PLT and logMAR BCVA at months 3 and 6 after treatment (r = − 0.549, P < 0.001; r = − 0.087, P < 0.001).ConclusionIntravitreal injection of conbercept is an effective treatment for CRVO-ME. With 6 months of follow-up, logMAR BCVA and CST, MV, PLT, ONLT, DEZ improved. PLT was negatively correlated with the visual function in CRVO-ME patients after conbercept treatment, which may be a predictor of vision recovery in patients with CRVO-ME.

ATF6 is required for efficient rhodopsin clearance and retinal homeostasis in the P23H rho retinitis pigmentosa mouse model

Retinitis Pigmentosa (RP) is a blinding disease that arises from loss of rods and subsequently cones. The P23H rhodopsin knock-in (P23H-KI) mouse develops retinal degeneration that mirrors RP phenotype in patients carrying the orthologous variant. Previously, we found that the P23H rhodopsin protein was degraded in P23H-KI retinas, and the Unfolded Protein Response (UPR) promoted P23H rhodopsin degradation in heterologous cells in vitro. Here, we investigated the role of a UPR regulator gene, activating transcription factor 6 (Atf6), in rhodopsin protein homeostasis in heterozygous P23H rhodopsin (Rho+/P23H) mice. Significantly increased rhodopsin protein levels were found in Atf6−/−Rho+/P23H retinas compared to Atf6+/−Rho+/P23H retinas at early ages (~ P12), while rhodopsin mRNA levels were not different. The IRE1 pathway of the UPR was hyper-activated in young Atf6−/−Rho+/P23H retinas, and photoreceptor layer thickness was unchanged at this early age in Rho+/P23H mice lacking Atf6. By contrast, older Atf6−/−Rho+/P23H mice developed significantly increased retinal degeneration in comparison to Atf6+/−Rho+/P23H mice in all retinal layers, accompanied by reduced rhodopsin protein levels. Our findings demonstrate that Atf6 is required for efficient clearance of rhodopsin protein in rod photoreceptors expressing P23H rhodopsin, and that loss of Atf6 ultimately accelerates retinal degeneration in P23H-KI mice.

Analyses of the effects of persistent subretinal fluid on visual/anatomic outcomes according to the type of macular neovascularization during the relaxed treat-and-extend protocol in age-related macular degeneration patients

BackgroundTo analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients.MethodsPatients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the ‘persistent SRF (+) group’. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type.ResultsSeventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (−) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type.ConclusionsUsing a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.

Retinal and choroidal thickness measurements in obstructive sleep apnea: impacts of continuous positive airway pressure treatment.

To examine retinal and choroidal thicknesses in individuals with obstructive sleep apnea (OSA) and determine the impacts of continuous positive airway pressure (CPAP) treatment. Prospective follow-up study conducted at a university hospital. 40 patients with OSA, 28 treated with CPAP, and 12 untreated, were enrolled immediately after diagnosis and graded according to the apnea hypopnea index (AHI) determined in an overnight polysomnography. Inclusion criteria were a new diagnosis of OSA and CPAP indicated. Participants underwent a full ophthalmologic examination including optical coherence tomography (OCT) at the peripapillary, macular, and choroidal levels and the same examination 3months later. Outcome measures were peripapillary retinal nerve fiber layer (RNFL), total retinal (TRT), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), photoreceptor layer (PL), and choroidal thicknesses. At 3months, RGCL thickness was reduced at the inner nasal macula segment in the no-CPAP group (P = 0.016). In + CPAP, increases were produced in RNFL thickness (5/6 segments) and TRT (7/ 9 segments), while choroidal thinning was observed temporally (P = 0.003). At baseline, positive correlation was detected between choroidal thickness and AHI (r = 0.352, P = 0.005) and between IPL thickness (7/9 segments) and AHI (r = 0.414, P < 0.001). Initial retinal and choroidal thickening was followed by RGCL thinning over 3months. In patients receiving CPAP, we observed no thinning of any retinal layer and normalization of choroidal thickness.

The Impact of Glycemic Control on Retinal Photoreceptor Layers and Retinal Pigment Epithelium in Patients With Type 2 Diabetes Without Diabetic Retinopathy: A Follow-Up Study.

AimsTo establish the sequential changes by glycemic control in the mean thickness, volume and reflectance of the macular photoreceptor layers (MPRLs) and retinal pigment epithelium in patients with type 2 diabetes without diabetic retinopathy.MethodsThirty-one poorly controlled (HbA1c > 8.0%) patients with type 2 diabetes without diabetic retinopathy undergoing glycemic control and 39 control subjects with normal HbA1c levels (< 5.9%) underwent periodical full medical, neurological and ophthalmological examinations over 2 years. Glycemic variability was evaluated by standard deviation and coefficient of variation of monthly measured HbA1c levels and casual plasma glucose. 3D swept source-optical coherence tomography (OCT) and OCT-Explorer-generated enface thickness, volume and reflectance images for 9 subfields defined by Early Treatment Diabetic Retinopathy Study of 4 MPRLs {outer nuclear layer, ellipsoid zone, photoreceptor outer segment (PROS) and interdigitation zone} and retinal pigment epithelium were acquired every 3 months.ResultsGlycemic control sequentially restored the thickness and volume at 6, 4 and 5 subfields of outer nuclear layer, ellipsoid zone and PROS, respectively. The thickness and volume of outer nuclear layer were restored related to the decrease in HbA1c and casual plasma glucose levels, but not related to glycemic variability and neurological tests. The reflectance of MPRLs and retinal pigment epithelium in patients was marginally weaker than controls, and further decreased at 6 or 15 months during glycemic control. The reduction at 6 months coincided with high HbA1c levels.ConclusionGlycemic control sequentially restored the some MPRL thickness, especially of outer nuclear layer. In contrast, high glucose during glycemic control decreased reflectance and may lead to the development of diabetic retinopathy induced by glycemic control. The repeated OCT examinations can clarify the benefit and hazard of glycemic control to the diabetic retinopathy.

Evaluation of the subfoveal choroidal and outer retinal layer thickness in obese women

ABSTRACT Clinical relevance Obesity has become one of the most important health problems of today with its increasing prevalence. With the development of retinal imaging systems, obesity has been observed to be associated with changes in outer retinal layers and choroid in women. Background The aim of this study was to examine retinal layer parameters and their relationship with body mass index in obese women. Methods The study included 197 eyes of 197 women, of whom 44 were normal‐weight, 40 were overweight, 40 were class 1 obese, 38 were class 2 obese, and 35 were morbidly obese. The thickness of the choroid was measured manually using an enhanced‐depth imaging optical coherence tomography scanning program. Results The mean choroidal thickness values in five locations were lower than those of normal‐weight, overweight, class 1, and class 2 obese women, in morbidly obese women (p < 0.05 for all). Subfoveal outer retinal layer thickness and specific sublayer thickness of the photoreceptor layer values were significantly lower in morbidly obese women than in normal‐weight women, but there were no statistically significant differences between the groups in retinal pigment epithelium thickness and Bruch’s membrane thickness (p = 0.001, p < 0.001, p = 1.00, and p = 0.101, respectively). Furthermore, there were significant negative relationships between body mass index and subfoveal choroidal thickness, subfoveal outer retinal layer thickness, and specific sublayer thickness of the photoreceptor layer values (r = −0.327, p < 0.001; r = −0.259, p < 0.001; and r = −0.281, p < 0.001, respectively). Conclusions Morbid obesity was associated with a thinner choroid, subfoveal outer retinal layer, and specific sublayer thickness of the photoreceptor layer in women. Furthermore, retinal hypoxia associated with morbid obesity may be related to a decrease in photoreceptor layer thickness. Thinning of the outer retinal layer may also lead to atrophy of the cone sheath.