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Purpose: To describe the clinical and multimodal imaging features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor therapy, in eyes with macular neovascularization., Methods: Retrospective, observational case series of 14 eyes (14 patients, 7 men) imaged with eyes (14 patients, 7 men) were imaged with spectral-domain optical coherence tomography, and either fluorescein angiography or optical coherence tomography angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity assessments., Results: The mean age was 75 ± 13 (range: 45-96) years, with mean follow-up duration of 27 ± 21 (range: 1-56) months. Neovascular age-related macular degeneration was found in 71% (10/14) eyes. Type 2 macular neovascularization lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved after intravitreal antivascular endothelial growth factor therapy in all eyes. The baseline best-corrected visual acuity improved from logarithm of the minimum angle of resolution 0.84 ± 0.32 (Snellen equivalent 20/138) to logarithm of the minimum angle of resolution 0.48 ± 0.31 (Snellen equivalent 20/60) at the last follow-up, with treatment of the macular neovascularization., Conclusion: Type 2 macular neovascularization and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal antivascular endothelial growth factor therapy results in rapid resolution of BDs and visual improvement in most eyes.

Aims/introduction: Diabetic polyneuropathy (DPN) and diabetic retinopathy (DR) are traditionally regarded as microvascular complications. However, these complications may share similar neurodegenerative pathologies. Here we evaluate the correlations in the severity of DPN and changes in the thickness of neuroretinal layers to elucidate whether these complications exist at similar stages of progression., Materials and Methods: A total of 43 patients with type 2 diabetes underwent a nerve conduction study (NCS), a macular optical coherence tomography, and a carotid artery ultrasound scan. Diabetic polyneuropathy was classified according to Baba's classification using NCS. The retina was automatically segmented into four layers; ganglion cell complex (GCC), inner nuclear layer/outer plexiform layer (INL/OPL), outer nuclear layer/photoreceptor inner and outer segments, and retinal pigment epithelium (RPE). The thickness of each retinal layer was separately analyzed for the fovea and the parafovea., Results: Fourteen patients were classified as having moderate to severe diabetic polyneuropathy. The thicknesses of the foveal and parafoveal INL/OPL increased in patients with diabetic polyneuropathy compared with patients without. The thickness of the parafoveal retinal pigment epithelium decreased in patients with diabetic polyneuropathy. The thinning of parafoveal ganglion cell complex and foveal and parafoveal retinal pigment epithelium were positively correlated with deterioration of nerve functions in the nerve conduction study, but the thickening of INL/OPL was positively correlated with the nerve function deterioration. The thinning of parafoveal ganglion cell complex and foveal retinal pigment epithelium were positively correlated with the thickening of the carotid intima-media., Conclusions: Depending on the progression of diabetic polyneuropathy, the ganglion cell complex and retinal pigment epithelium became thinner and the INL/OPL became thicker. These retinal changes might be noteworthy for pathological investigations and for the assessment of diabetic polyneuropathy and diabetic retinopathy., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Purpose: We sought to investigate the ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with nonexudative age-related macular degeneration., Methods: We classified eyes into four categories-pachydrusen, soft drusen, subretinal drusenoid deposit (SDD), and soft drusen with SDD-and compared the baseline mean macular GCIPL thickness according to the Early Treatment Diabetic Retinopathy Study grid and its change between groups., Results: We classified 53, 29, 36, and 34 eyes into the four categories, respectively. The mean GCIPL thickness values in the 3-mm area were 82.61 ± 9.54 µm for the pachydrusen group, 79.11 ± 10.26 µm for the soft drusen group, 77.72 ± 6.04 µm for the SDD group, and 71.63 ± 8.69 µm for the soft drusen with SDD group (P < 0.001). The soft drusen with the SDD group showed a greater change in GCIPL thickness (-2.50 ± 0.29 µm/year) in the 3-mm area as compared with the pachydrusen group (-0.18 ± 0.35 µm/year), soft drusen group (-0.55 ± 0.36 µm/year), and SDD group (-0.55 ± 0.37) (all P < 0.001)., Conclusion: The GCIPL thickness varied according to the type of nonexudative age-related macular degeneration. The thinner baseline GCIPL and its greater change in eyes with soft drusen with SDD may suggest that these eyes are experiencing more prominent neuroretinal degeneration in the central 3-mm area than those in the other groups.

Accumulation of misfolded host proteins is central to neuropathogenesis of numerous human brain diseases including prion and prion-like diseases. Neurons of retina are also affected by these diseases. Previously, our group and others found that prion-induced retinal damage to photoreceptor cells in mice and humans resembled pathology of human retinitis pigmentosa caused by mutations in retinal proteins. Here, using confocal, epifluorescent and electron microscopy we followed deposition of disease-associated prion protein (PrPSc) and its association with damage to critical retinal structures following intracerebral prion inoculation. The earliest time and place of retinal PrPSc deposition was 67 days post-inoculation (dpi) on the inner segment (IS) of cone photoreceptors. At 104 and 118 dpi, PrPSc was associated with the base of cilia and swollen cone inner segments, suggesting ciliopathy as a pathogenic mechanism. By 118 dpi, PrPSc was deposited in both rods and cones which showed rootlet damage in the IS, and photoreceptor cell death was indicated by thinning of the outer nuclear layer. In the outer plexiform layer (OPL) in uninfected mice, normal host PrP (PrPC) was mainly associated with cone bipolar cell processes, but in infected mice, at 118 dpi, PrPSc was detected on cone and rod bipolar cell dendrites extending into ribbon synapses. Loss of ribbon synapses in cone pedicles and rod spherules in the OPL was observed to precede destruction of most rods and cones over the next 2-3 weeks. However, bipolar cells and horizontal cells were less damaged, indicating high selectivity among neurons for injury by prions. PrPSc deposition in cone and rod inner segments and on the bipolar cell processes participating in ribbon synapses appear to be critical early events leading to damage and death of photoreceptors after prion infection. These mechanisms may also occur in human retinitis pigmentosa and prion-like diseases, such as AD.

Purpose: Macular edema is a common retinal disease which may leave important anatomical and functional sequelaes. Directional fundus imaging consists of comparing on- and off-axis images to reveal angle-dependent reflectance properties of fundus structures, which may be related to misaligned photoreceptors. Here, we analyzed directional optical coherence tomography (OCT) and flood-illumination adaptive optics ophthalmoscopy images to detect evidence of misaligned photoreceptors following macular edema., Methods: Transversal, observational study. Nine patients having recovered a normal macular profile after macular edema due to retinal vein occlusion were included. For each patient, a reference OCT scan (i.e., with the incident beam normal to the fovea) was acquired, and off-axis scans were then acquired by laterally shifting the entry pupil. In addition, in four of these eyes, directional adaptive optics ophthalmoscopy documented the directional variations of cone metrics., Results: Included patients comprised two women and seven men (age range, 19-76 years). Reference OCT scans showed patchy attenuation of the cone outer segment tips and to a lesser extent of the inner segment/outer segment lines in all, but two eyes; these. Increased intensity of the cone outer segment tips and inner segment/outer segment lines could be observed on off-axis scans. Accordingly, fusion images showed 66% average reduction of the length of cone outer segment tips attenuation. In two cases, although reference scans showed continuity of outer bands, focal attenuation was evidenced in off-axis images. Directional adaptive optics ophthalmoscopy imaging showed a strong directional variability of cone counts in these areas, ranging from near absence to roughly two-third of reference values. In each case, directional variations of cone counts paralleled those of the reflectance of outer bands., Conclusion: After macular edema, focal attenuations of the inner segment/outer segment and of the cone outer segment tips lines may be present on OCT. These areas may show a strong directional variability by both OCT and adaptive optics ophthalmoscopy, suggesting that misaligned photoreceptor outer segments contribute to such features. The evaluation of outer retinal damage following macular edema should therefore take into account the optical Stiles-Crawford effect to disambiguate missing from misaligned cones.

Purpose: To validate the efficacy of a fully automatic, deep learning-based segmentation algorithm beyond conventional performance metrics by measuring the primary outcome of a clinical trial for macular telangiectasia type 2 (MacTel2)., Design: Evaluation of diagnostic test or technology., Participants: A total of 92 eyes from 62 participants with MacTel2 from a phase 2 clinical trial (NCT01949324) randomized to 1 of 2 treatment groups METHODS: The ellipsoid zone (EZ) defect areas were measured on spectral domain OCT images of each eye at 2 time points (baseline and month 24) by a fully automatic, deep learning-based segmentation algorithm. The change in EZ defect area from baseline to month 24 was calculated and analyzed according to the clinical trial protocol., Main Outcome Measure: Difference in the change in EZ defect area from baseline to month 24 between the 2 treatment groups., Results: The difference in the change in EZ defect area from baseline to month 24 between the 2 treatment groups measured by the fully automatic segmentation algorithm was 0.072±0.035 mm 2 (P = 0.021). This was comparable to the outcome of the clinical trial using semiautomatic measurements by expert readers, 0.065±0.033 mm 2 (P = 0.025)., Conclusions: The fully automatic segmentation algorithm was as accurate as semiautomatic expert segmentation to assess EZ defect areas and was able to reliably reproduce the statistically significant primary outcome measure of the clinical trial. This approach, to validate the performance of an automatic segmentation algorithm on the primary clinical trial end point, provides a robust gauge of its clinical applicability., (Copyright © 2019 American Academy of Ophthalmology. All rights reserved.)

This study was aimed to investigate morphological alteration of the retina with N-methyl-D-aspartate (NMDA)-induced injury in rabbits by optical coherence tomography (OCT). The right and left eyes of a total of 12 rabbits received single-intravitreal injection of vehicle and NMDA, respectively. Four out of the 12 animals underwent OCT and quantification of plasma microRNA repeatedly (4, 48, and 168 hr after dosing), followed by ocular histopathology at the end of the study. Ocular histopathology was also conducted in the eyes collected 4 or 48 hr after dosing from 4 animals at each time period. OCT revealed hyper-reflective ganglion cell complex and thickened inner retina in NMDA-treated eyes 4 hr after dosing; the inner retina shifted to thinning at later time points. The eyes given NMDA also exhibited greater thickness of the outer retina, which contains photoreceptors, after treatment, and thickened and obscured ellipsoid zone 168 hr after dosing. The plasma levels of miR-182 and miR-183, which are known to be highly expressed in photoreceptors, were higher 4 hr after dosing than pre-dosing values. Histopathologically, NMDA-induced inner retinal damage was confirmed: single-cell necrosis was observed in the ganglion cell layer and the inner nuclear layer 4 hr after dosing, the incidence of which decreased thereafter. At 168 hr after dosing, reduced number of ganglion cells was noted. No change was histopathologically observed in the outer retina. In conclusion, our results suggest involvement of photoreceptors in NMDA-induced inner retinal injury. Additionally, OCT revealed acute inner retinal findings suggestive of temporary edema.

Objective: To investigate whether inner nuclear layer (INL) thickness as assessed with optical coherence tomography differs between patients with progressive MS (P-MS) according to age and disease activity., Methods: In this retrospective longitudinal analysis, differences in terms of peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer + inner plexiform layer (GCIPL), INL and T1/T2 lesion volumes (T1LV/T2LV) were assessed between 84 patients with P-MS and 36 sex- and age-matched healthy controls (HCs) and between patients stratified according to age (cut-off: 51 years) and evidence of clinical/MRI activity in the previous 12 months RESULTS: pRNFL and GCIPL thickness were significantly lower in patients with P-MS than in HCs ( p = 0.003 and p < 0.0001, respectively). INL was significantly thicker in patients aged < 51 years compared to the older ones and HCs (38.2 vs 36.5 and 36.7 μm; p = 0.038 and p = 0.04, respectively) and in those who presented MRI activity (new T2/gadolinium-enhancing lesions) in the previous 12 months compared to the ones who did not and HCs (39.5 vs 36.4 and 36.7 μm; p = 0.003 and p = 0.008, respectively). Recent MRI activity was significantly predicted by greater INL thickness (Nagelkerke R 2 0.36, p = 0.001)., Conclusions: INL thickness was higher in younger patients with P-MS with recent MRI activity, a criterion used in previous studies to identify a specific subset of patients with P-MS who best responded to disease-modifying treatment. If this finding is confirmed, we suggest that INL thickness might be a useful tool in stratification of patients with P-MS for current and experimental treatment choice., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose: To investigate correlations between the inner-retinal irregularity index and interdigitation zone (IZ) defects preidiopathic and postidiopathic epiretinal membrane (ERM) surgery., Methods: The authors retrospectively assessed ophthalmic parameters in 89 eyes of 89 patients with ERM. They divided patients into the no-IZ defect (51, 57%) and IZ defect (38, 43%) groups. The IZ defect group was subdivided into recovered (22, 58%) and remaining IZ defect (16, 42%) subgroups, according to IZ recovery status at final examination. The inner-retinal irregularity index of each group was measured before and 1-, 3-, and 6-month postsurgery., Results: Clinical characteristics were similar in both groups. The IZ defect group had a statistically significant higher inner-retinal irregularity index than the no-IZ defect group before (P = 0.023), but not after ERM surgery. The inner-retinal irregularity index of the recovered and remaining IZ defect subgroups was similar before surgery, but differed markedly 6 months after surgery (P = 0.048). Changes in the inner-retinal irregularity index quantitatively correlated with IZ defect size before and after ERM surgery (P < 0.001)., Conclusion: The inner-retinal irregularity index differed significantly according to the IZ status and also correlated with the IZ defect before and after ERM surgery. The inner-retinal irregularity index may reflect the outer-retinal damage in ERM.

Purpose: To compare retinal photoreceptor ellipsoid zone (EZ) intensity between normal eyes and those with different stages of glaucoma., Design: Retrospective cross-sectional study., Methods: The study included 37 normal, 38 preperimetric glaucoma, 39 mild-to-moderate glaucoma (visual field [VF] mean deviation [MD]: -7.7 ± 2.0 dB), and 36 severe glaucoma eyes (VF MD: -17.8 ± 3.2 dB). The subjects underwent high-resolution horizontal and vertical line scans through the fovea by spectral-domain optical coherence tomography (SD-OCT). Image processing software was employed to quantify the intensity of the first and second hyperreflective bands corresponding with the external limiting membrane (ELM) and EZ. In order to account for the brightness variation among scans, the relative EZ intensity as the ratio of the second to first reflective band (EZ/ELM) was determined., Results: The relative EZ intensity in severe glaucoma eyes was significantly lower than in mild-to-moderate glaucoma eyes (2.46 ± 0.38 vs 3.15 ± 0.43, P < .001); also, it was lower in mild-to-moderate than in preperimetric glaucoma eyes (3.15 ± 0.43 vs 3.86 ± 0.44, P < .001). However, the comparison between preperimetric glaucoma and normal eyes showed no significant difference (3.86 ± 0.44 vs 4.06 ± 0.40, P = .751). In 75 glaucomatous eyes with VF defect, there was a significant correlation between relative EZ intensity and VF MD (r = 0.83 and P < .001)., Conclusions: According to SD-OCT, relative EZ intensity reduction occurs in the mild-to-moderate and severe glaucoma stages. These findings suggest, at least provisionally, that in the course of glaucoma progression, mitochondrial changes in the inner segments of photoreceptors occur. Further investigation is warranted to evaluate the potential clinical significance of EZ intensity reduction in glaucoma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Assessment of the diagnostic ability of segmented macular inner retinal layer thickness and peripapillary retinal nerve fiber layer (pRNFL) measured by spectral-domain optical coherence tomography (SD-OCT) in patients with normal-tension (NT) and high-tension (HT) perimetric and preperimetric glaucoma., Methods: The 212 participants included 45 healthy subjects, 55 patients with ocular hypertension, 56 patients with preperimetric glaucoma, and 56 patients with perimetric glaucoma. The preperimetric and perimetric groups were further subdivided into NT and HT groups. Sectoral and global thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (mGCL), inner plexiform layer (mIPL), ganglion cell complex (mGCC), and pRNFL were measured using SD-OCT (Spectralis, Heidelberg Engineering, Germany). Diagnostic performance was ascertained by sectoral and global comparison of the sensitivities at specificity ≥ 95%., Results: For all layers, the largest thickness decrease was reported in the HT perimetric group. In all groups, the sensitivities of mGCL showed a comparable diagnostic value to pRNFL in order to distinguish between healthy subjects and glaucoma patients. In the perimetric group, mGCL (85.7%) exhibited higher sensitivities than mRNFL (78.6%) and mGCC (78.6%). Both mRNFL and pRNFL demonstrated equal diagnostic performance in the HT perimetric group (88.5 and 96.2%), in the NT groups, mRNFL was inferior to all other layers., Conclusion: The sensitivities of mGCL and mRNFL were comparable to the sensitivities of pRNFL. In clinical application, mGCL and mRNFL, with a focus on the temporal and inferior sectors, may provide a convincing supplementation to pRNFL., Clinical Trial Registration: Erlangen Glaucoma Registry www.clinicaltrials.gov ID: NCT00494923.

Purpose: To study the qualitative and quantitative features of choroidal neovascular (NV) membranes in age-related macular degeneration using optical coherence tomography angiography in patients with active and quiescent NV lesions before and after treatment with anti-vascular endothelial growth factor., Methods: Macular optical coherence tomography angiography images were obtained using RTVue XR Avanti with AngioVue. Morphologic features and quantitative measurements of the NV lesion were analyzed using en face projection images. The NV lesion was subdivided into inner segment and outer fringe for further fractal dimension analysis., Results: In a series of 31 eyes, 11 eyes with active NV lesions at baseline and after consecutive follow-up after treatment with anti-vascular endothelial growth factor therapy and 20 eyes with quiescent NV lesions were included in this study. Morphologically, all the quiescent NV lesions versus 63.6% of the active NV lesions demonstrated a prominent central vessel and active leasions demonstrated a greater rate of small vessels branching (82%) and peripheral arcades (82%) than quiescent lesions (30% and 40% respectively) and this was statistically significant. The lesion area and vessel density was not statistically significantly different after treatment or versus quiescent lesions although the latter lesions were reduced in area. Lesion pattern complexity measured by the fractal dimension was statistically significantly lower in the inner part of the lesion after treatment and statistically significantly lower in the total lesion of the quiescent NV compared with the active NV., Conclusion: Optical coherence tomography angiography is a new, noninvasive imaging modality that can be used to perform qualitative and quantitative analyses of NV lesions. In the future, OCT angiography may provide biomarkers of activity and guide the evaluation and treatment and monitoring of neovascularization in age-related macular degeneration.

In healthy beings, age is the ultimate reason of cellular malfunction and death. In the rat retina, age causes a functional decline and loss of specific neuronal populations. In this regard, controversial conclusions have been reported for the innermost retina. Here, we have studied the albino and pigmented retina for the duration of the rat life-span. Independent of age (21 days-22 months), the electroretinographic recordings and the volume of the retina and its layers are smaller in albinos. Functionally, aging causes in both strains a loss of cone- and rod-mediated responses. Anatomically, cell density decreases with age because the retina grows linearly with time; no cell loss is observed in the ganglion cell layer; and only in the pigmented rat, there is a decrease in cone photoreceptors. In old animals of both strains, there is gliosis in the superior colliculi and a diminution of the area innervated by retinal ganglion cells. In conclusion, this work provides the basis for further studies linking senescence to neurodegenerative retinal diseases., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To report the clinical characteristics of asymptomatic cases with RP1L1 gene mutations in four families with occult macular dystrophy (OMD)., Methods: Four asymptomatic cases from four families were selected from a cohort of 40 subjects (16 families) with RP1L1 pathogenic variants. Clinical data of the four asymptomatic cases and three symptomatic patients in the same families were reviewed. The three asymptomatic cases did not have any visual symptoms in either eye, and one was unilaterally affected. Ophthalmologic examinations, including spectral-domain optical coherence tomography (OCT) were performed, and the morphologic characteristics of the photoreceptor layer of the asymptomatic cases were compared to those of the symptomatic patients within the same family., Results: The OCT images demonstrated photoreceptor abnormalities in the parafoveal regions in all of the four asymptomatic cases (i.e., absence of the interdigitation zone and blurring of the ellipsoid zone). However, these microstructures were preserved at the foveal center. The longitudinal reflectivity profiles clearly identified this distinct pattern in the asymptomatic cases. In contrast, no distinct abnormalities were detected by other examinations including perimetry, fundus autofluorescence images, and multifocal electroretinograms (ERGs)., Conclusions: The sparing of the central foveal photoreceptor layer accounts for the well-preserved visual acuity in the asymptomatic patients. The sparing may represent either the initial phase of typical OMD or a subtype of macular lesion associated with OMD. It is necessary to examine asymptomatic subjects in families with OMD because some of them may progress to the typical phenotype of OMD.

Purpose: To evaluate the rate of change in ganglion cell-inner plexiform layer (GCIPL) thickness measured by optical coherence tomography (OCT) using a trend-based approach in early-stage glaucomatous eyes with disc hemorrhage (DH) and to compare the GCIPL thinning rate with that in glaucomatous eyes without DH., Methods: This prospective observational study included 46 patients with early-stage open-angle glaucoma and DH who underwent serial spectral-domain OCT measurements for at least 30 months. The GCIPL thinning rate was determined in the global, superior, or inferior hemiretinas and in six macular sectors by linear regression and was compared between glaucomatous eyes with DH and fellow glaucomatous eyes without DH and between glaucomatous eyes with DH and non-DH glaucomatous control eyes., Results: The GCIPL thinning rate (mean ± standard deviation) was significantly more rapid in glaucomatous eyes with DH than in fellow eyes without DH in the inferior hemiretina (-1.07 ± 0.75 vs. -0.44 ± 0.54 μm/y, P = 0.001), inferotemporal sector (-1.13 ± 1.00 vs. -0.61 ± 0.66 μm/y, P = 0.028), and inferior sector (-1.33 ± 0.79 vs. -0.42 ± 0.78 μm/y, P < 0.001). The GCIPL thinning rate was significantly more rapid in glaucomatous eyes with DH than in glaucomatous controls without DH in the global area (-0.78 ± 0.85 vs. -0.32 ± 0.48 μm/y, P = 0.002), the inferior hemiretina (-1.00 ± 0.94 vs. -0.37 ± 0.67 μm/y, P < 0.001), and the inferotemporal sector (-1.31 ± 1.07 vs. -0.34 ± 0.75 μm/y, P < 0.001)., Conclusions: The GCIPL thinning rate on OCT was significantly more rapid in glaucomatous eyes with DH than in fellow glaucomatous eyes without DH or glaucomatous control eyes without DH. DH could be associated with progression of glaucoma in terms of GCIPL thinning.

Purpose: To compare the foveal characteristics in fellow eyes (FE) of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes with eyes of healthy controls., Methods: Forty-seven FE and 52 eyes of 52 age- and sex-matched healthy controls were studied. Quantitative assessment of the dome-shaped appearance of the hyperreflective lines that represent external limiting membrane (ELM&#95;bulge) and inner outer segment junctions (IS/OS&#95;bulge) were made by optical coherence tomography (OCT) images. Inner retinal complex thickness (IRCT) was quantitatively assessed at 1000 and 2000 μm of the foveal center in nasal and temporal quadrants. Presence of alterations in the inner retinal outer layers and central foveal thickness (CFT) were also analyzed., Results: Significantly lower ELM&#95;bulge (p < 0.0001; Mann-Whitney test) and IS/OS&#95;bulge (p < 0.001; student t test) and higher cases with COST alterations, expressed as a diffuse line (p < 0.006; Chi 2 test) were found in FE than control eyes. IRCT were significantly reduced in FE at all the studied locations when comparing to control eyes (p < 0.05; student t test), maintaining anatomical proportionality among locations., Conclusion: FE without pathologic vitreomacular interactions seems to present some central cone alterations that may be related to other causes than vitreomacular traction.

PurposeTo investigate the retinal structural changes in endophthalmitis and their association with visual outcome.Patients and methodsForty-five eyes of 45 patients diagnosed with endophthalmitis were included. Spectral domain optical coherence tomography (SD-OCT) was performed after inflammation was controlled. The relationship between SD-OCT features and best-corrected visual acuity (BCVA) at the last follow-up was analyzed.ResultsThe structural changes included inner segment ellipsoid (ISe) disruption (49%), atrophy of retinal inner layers (24%), epimacular membrane (24%), and macular edema (24%). BCVA was worse in patients with ISe disruption (P=0.005) and retinal inner layers' atrophy (P=0.004) compared with those without. There was no significant difference of BCVA between the patients with and without epimacular membrane, or intraretinal cysts. Multivariate regression showed that atrophy of retinal inner layers (b=0.41±0.17, P=0.022) was the only independent factor associated with BCVA.ConclusionAtrophy of retinal inner layers is associated with visual impairment in endophthalmitis, despite successful management.

Purpose: To compare morphologic changes on en face images derived from wide-field swept-source optical coherence tomography (ssOCT) to hypo- and hyperautofluorescent (hypoAF, hyperAF) areas on short-wavelength autofluorescence (SW-AF), and near-infrared (NIR)-AF in recessive Stargardt disease (STGD1)., Methods: Wide-field ssOCT cube scans were obtained from 16 patients (16 eyes). Averaged B-scans and SW-AF images were obtained using Spectralis HRA+OCT. NIR-AF images were obtained from 6 eyes. The inner/outer segment (IS/OS), OS/RPE, and RPE/Bruch's membrane boundaries were segmented, and en face slab images generated. A subRPE slab image was used to measure the abnormal RPE area, and an IS/OS slab image, the IS/OS junction loss area. These were compared to hypo- and abnormal SW-AF areas, and hypoNIR-AF areas. A preRPE(OS) slab image was used to evaluate the spatial and intraretinal locations of flecks., Results: For all eyes, RPE atrophy was visualized as a central hyperreflective area on the subRPE slab, and IS/OS junction loss as an abnormal reflective area on the IS/OS slab; the latter was significantly larger (P = 0.04). There was good agreement between the hyperreflective area on the subRPE slab image and hypoSW-AF area, and between the abnormal reflective area on the IS/OS slab and hypo-hyperSW-AF area; the hypoNIR-AF area indicated that the hyperreflective area on the subRPE slab underestimated RPE atrophy. The spatial locations of hyperreflective flecks on the en face preRPE(OS) slab image corresponded to those on the SW-AF images., Conclusions: Wide-field en face OCT imaging has the potential to be a clinically useful tool for the management of STGD1.

Purpose: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene, and refractive error in IRDs may provide insight herein., Design: Case-control study., Methods: Study Population: Total of 302 patients with IRD from 2 ophthalmogenetic centers in the Netherlands. Reference Population: Population-based Rotterdam Study-III and Erasmus Rucphen Family Study (N = 5550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression., Results: Bipolar cell-related dystrophies were associated with the highest risk of SE high myopia 239.7; odds ratio (OR) mild hyperopia 263.2, both P < .0001; SE -6.86 diopters (D) (standard deviation [SD] 6.38), followed by cone-dominated dystrophies (OR high myopia 19.5, P < .0001; OR high hyperopia 10.7, P = .033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P < .0001; OR high hyperopia 9.7, P = .001; SE -2.27 D [SD 4.65]), and retinal pigment epithelium (RPE)-related dystrophies (OR low myopia 2.7; P = .001; OR high hyperopia 5.8; P = .025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia and in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia., Conclusions: Refractive errors, in particular myopia, are common in IRD. The bipolar synapse and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate the relationship between ganglion cell complex (GCC) thickness and photoreceptor alterations in eyes with intermediate age-related macular degeneration (AMD)., Design: Retrospective case-control study., Methods: We collected data from 68 eyes with intermediate AMD from 68 patients with spectral-domain optical coherence tomography (SDOCT) imaging. A control group of 50 eyes from 50 healthy subjects was included for comparison. Our main outcome measures for comparison between groups were (1) the average and minimum GCC thickness and (2) the "normalized" reflectivity of the ellipsoid zone (EZ) en face image., Results: The average and minimum GCC thicknesses were thinner in AMD patients (69.54 ± 9.30 μm and 63.22 ± 14.11 μm, respectively) than in healthy controls (78.57 ± 6.28 μm and 76.28 ± 6.85 μm, P < .0001 and P < .0001, respectively). Agreement was found to be excellent in the "normalized" EZ reflectivity assessment (intraclass correlation coefficient = 0.986, coefficient of variation = 1.11). The EZ "normalized" reflectivity was 0.67 ± 0.11 in controls and 0.61 ± 0.09 in the AMD group (P = .006). In univariate analysis, EZ "normalized" reflectivity was found to have a significant direct relationship with average (P < .0001) and minimum (P < .0001) GCC thickness in AMD patients, but not in controls (P = .852 and P = .892, respectively)., Conclusions: Eyes with intermediate AMD exhibit GCC thinning, as well as a reduced EZ "normalized" reflectivity, and these parameters are correlated. This study supports the concept of postreceptor retinal neuronal loss as a contributor to retinal thinning in intermediate AMD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate the differences between macular inner retinal layers and peripapillary retinal nerve fibre layer (pRNFL) thickness in Chinese patients with neuromyelitis spectrum optic neuritis (NMOSD-ON) and isolated optic neuritis (ION) with only one episode., Methods: This cross-sectional study included 35 patients (35 eyes) with NMOSD-ON (NMO-IgG seropositive) and 46 patients (46 eyes) with ION after one episode. Spectral domain optical coherence tomography (SD-OCT) was used to quantify pRNFL, macular RNFL (mRNFL), ganglion cell and inner plexiform layers (GCIPL) and inner nuclear layer (INL) thickness using an automated algorithm. Differences in OCT parameters between NMOSD-ON and ION were compared after adjusting for age, sex and disease duration., Results: The pRNFL and mRNFL in some locations (average pRNFL, nasal pRNFL, nasal inferior (NI) pRNFL, nasal/temporal (N/T) ratio pRNFL, average mRNFL, inner temporal mRNFL, outer nasal mRNFL and outer temporal mRNFL) in NMOSD-ON differed significantly from those in ION (all p < 0.05). These parameters had moderate diagnostic accuracy, with area under curves (AUCs) ranging from 0.684 to 0.762 for pRNFL and from 0.660 to 0.700 for mRNF. The thickness of GC-IPL and INL in all sectors was similar in NMOSD-ON and ION (p > 0.05). This study and our meta-analysis of four previous studies obtained consistent results, with pooled mean difference (MD) -10.4 μm (95% CI: -12.4 to -8.4, p < 0.001) for pRNFL, -1.5 μm (95% CI: -3.5 to 0.6, p = 0.158) for mRNFL and 0.2 μm (95% CI: -0.4 to 0.9, p = 0.490) for GC-IPL, respectively., Conclusions: Neuromyelitis spectrum optic neuritis (NMOSD-ON) patients had more pRNFL and mRNFL loss compared to ION patients after one episode. Spectral domain optical coherence tomography (SD-OCT) may help to distinguish NMOSD-ON from ION with only moderate diagnostic accuracy., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate alterations on optical coherence tomography angiography (OCT-A) and quantitatively assess alterations in the ellipsoid zone (EZ) in eyes with macular telangiectasia type 2 (MacTel type 2)., Methods: The Observational Assessment of Visualizing and Analyzing Vessels With Optical Coherence Tomography Angiography in Retinal Diseases study is an institutional review board-approved prospective, observational study investigating OCT-A in macular disease. Patients underwent spectral-domain (SD)-OCT and OCT-A imaging at a single visit. SD-OCT data were analyzed using a novel OCT EZ-mapping software to obtain linear, area, and volumetric measurements of the EZ-retinal pigment epithelium (RPE) complex across the macular cube. OCT-A retinal capillary density was measured using the Optovue Avanti split-spectrum amplitude-decorrelation angiography algorithm. EZ-RPE parameters were compared to age-matched, sex-matched controls., Results: Fourteen eyes of seven patients (mean age, 59 ± 6.5 years) were analyzed. Mean visual acuity was 20/45 (range, 20/20-20/150). EZ-RPE central foveal mean thickness was 27.8 ± 6.7 μm, EZ-RPE central foveal thickness was 22.1 ± 21.6 μm, EZ-RPE central foveal area was 0.17 ± 0.04 mm2, and EZ-RPE central subfield volume was 0.017 ± 0.012 mm3. Each of these measurements was significantly inversely correlated with visual acuity (P < 0.02). In addition, all of these measurements were significantly reduced compared to controls (all P ≤ 0.005). OCT-A showed a reduced parafoveal vessel density of 50.8% temporally compared to 53.8% nasally (P = 0.01) in the superficial vascular plexus. In the deep vascular plexus, similar findings were noted with a parafoveal vessel density of 56.7% temporally and 58.8% nasally (P = 0.01)., Conclusions: Abnormalities in EZ-RPE thickness, area, and volume are correlated with visual acuity in MacTel type 2, and may provide quantitative markers to measure disease progression and treatment response. OCT-A was a useful adjunct for determining disease severity.

Purpose: The purpose was to evaluate the effects of long-term anti-VEGF treatment on the retinal nerve fiber layer (RNFL) and retinal ganglion cell layer (RGCL) thickness for patients with neovascular AMD and glaucoma., Methods: Medical records of respective patients who had received more than 15 anti-VEGF injections were reviewed. Initial and latest SD-OCT macular scans were segmented and changes of the RNFL and RGCL thickness at the four outer ETDRS quadrants were evaluated. Secondary outcome measures included changes of visual field parameters seen in automated perimetry., Results: Sixteen patients were included (mean age 78 ± 6 years). The mean total number of anti-VEGF injections was 39 ± 16. The mean treatment duration was 6.1 ± 2.1 years. The mean IOP decreased from 18 ± 5 mmHg at baseline to 15 ± 5 mmHg at the last visit (p = 0.026). The mean RNFL thickness volume of the outer ETDRS quadrants (0.98 ± 0.18 mm 3 to 0.97 ± 0.18 mm 3 p = 0.61) and its average thickness (37.9 ± 7.3 μm to 37.2 ± 7.4 μm, p = 0.6) did not significantly change. However, the average RGCL thickness decreased significantly from 0.86 ± 0.12 mm 3 to 0.79 ± 0.11 mm 3 (p = 0.01), and from 27.7 ± 4.2 to 25.9 ± 3.7 μm (p = 0.01). Number of injections correlated with the RGCL change (r2 = 0.36, p = 0.01). The mean sensitivity, mean defect and absolute scotomata did not significantly change with p-values of 0.28, 0.21 and 0.07, respectively., Conclusion: Patients under long term treatment with anti-VEGF and concurrent glaucoma show significant decrease in macular RGLC volume. However, this decrease is comparable to reported RGCL decrease in patients under anti-VEGF treatment without underlying glaucoma and suggests that glaucoma patients may not be at a higher risk for losing macular RNFL and RGCL, at least if adequate control of intraocular pressure is maintained.

PurposeTo correlate the frequency and extent of simultaneous inadvertent internal limiting membrane (ILM) peeling during idiopathic epiretinal membrane (ERM) removal with characteristics of ERM adherence demonstrated on pre-operative spectral domain optical coherence tomography (SD-OCT).Patients and methodsThis is a prospective, observational, case series of patients undergoing pars plana vitrectomy for idiopathic ERM. Inner retina-ERM adhesion was categorized as focal, broad or complete in five anatomic locations at macular area based on preoperative SD-OCT findings. The extent of spontaneous ILM peeling was quantified on a scale 0-100% in each of the aforementioned anatomic locations by the operating surgeons who were masked to the OCT characteristics. All operations were recorded with a high definition recording system and the area of simultaneous ILM peel was quantified by a second masked observer. The final extent of spontaneous ILM peel was calculated as the average of the two scores.ResultsThirty consecutive subjects who underwent surgery for idiopathic ERM were included in the study. Evidence of simultaneous ILM peeling was identified in 80.3% of individuals. With regards to the type of ERM-macula adhesion, inadvertent ILM peel was observed in 70% of the patients who pre-operatively showed complete adhesion, in 43% with broad adhesion and in only 21% with focal adhesion (P<0.001). The extent of the spontaneous ILM peel during removal of ERM was also significantly dependent on the type of ERM-inner retina adhesion. Total simultaneous ILM peel was observed in 59% of locations with complete ERM-macula adhesion but only in 22% and 7% of locations with broad and focal adhesion respectively (P<0.001).ConclusionsSimultaneous ILM peel is a frequent occurrence during ERM surgery, especially when there is complete or broad ERM adherence to the macula. The type of ERM-inner retina adhesion represents a valid predictor of the extent of simultaneous ILM peel during removal of ERM. Thorough evaluation of preoperative OCT may be a useful tool in determining a safer, more simplistic strategy in ERM surgery.

Purpose: To characterize outer retina structure in best vitelliform macular dystrophy (BVMD) and to determine the effect of macular lesions on overlying and adjacent photoreceptors., Methods: Five individuals with BVMD were followed prospectively with spectral domain optical coherence tomography and confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). The AOSLO cone photoreceptor mosaic images were obtained within and around retinal lesions. Cone density was measured inside and outside lesions. In 2 subjects, densities were compared with published measurements acquired ∼2.5 years before. One subject was imaged 3 times over a 5-month period., Results: The AOSLO imaging demonstrated that photoreceptor morphology within BVMD retinal lesions was highly variable depending on the disease stage, with photoreceptor structure present even in advanced disease. The AOSLO imaging was repeatable even in severe disease over short-time and long-time intervals. Photoreceptor density was normal in retinal areas immediately adjacent to lesions and stable over ∼2.5 years. Mobile disk-like structures possibly representing subretinal macrophages were also observed., Conclusion: Combined confocal and nonconfocal split-detector AOSLO imaging reveals substantial variability within clinical lesions in all stages of BVMD. Longitudinal cellular photoreceptor imaging could prove a powerful tool for understanding disease progression and monitoring emerging therapeutic treatment response in inherited degenerations such as BVMD.

Purpose: To evaluate optical coherence tomography (OCT) modifications of outer retinal layers as determinants for functional recovery after surgery for idiopathic macular hole (IMH)., Methods: This prospective study included 23 eyes of 23 consecutive patients who underwent vitreoretinal surgery for IMH. We excluded patients with other retinal diseases. Baseline and follow-up evaluations at months 3 and 6 included complete ophthalmologic and instrumental evaluations. Functional evaluation was performed by Best Corrected Visual Acuity (BCVA) and Amsler test. Morphologic evaluation was performed by spectral-domain 3D-OCT (Topcon, Tokyo, Japan) for a deep analysis of retinal layers as well as central retinal thickness evaluation. A standard 23-G or 25-G vitreoretinal surgery was performed, completed by posterior hyaloid and inner limiting membrane peeling by means of vital dyes and gas tamponade. Statistical analysis was performed on collected data., Results: The mean BCVA increased significantly from 0.57 ± 0.25 logMAR at baseline to 0.34 ± 0.22 logMAR at month 6. Intraretinal layers modification showed a progressive recomposition of inner segment/outer segment layer in 91% of patients at month 6. Retinal layers recomposition showed a progressive increase in all patients during follow-up from the immediate postoperative control to the last 6-month visit., Conclusions: Optical coherence tomography examination appears useful to investigate visual recovery after macular hole surgery. To ensure postsurgical functional increase, recomposition of all retinal layers, in particular in the outer retina, is mandatory. This process could be slow and not immediately observable during follow-up examinations.

Purpose: To test the effects of rearing light intensity on retinal function and morphology in the retinoschisis knockout (Rs1-KO) mouse model of X-linked retinoschisis, and whether it affects functional outcome of RS1 gene replacement., Methods: Seventy-six Rs1-KO mice were reared in either cyclic low light (LL, 20 lux) or moderate light (ML, 300 lux) and analyzed at 1 and 4 months. Retinal function was assessed by electroretinogram and cavity size by optical coherence tomography. Expression of inward-rectifier K+ channel (Kir4.1), water channel aquaporin-4 (AQP4), and glial fibrillary acidic protein (GFAP) were analyzed by Western blotting. In a separate study, Rs1-KO mice reared in LL (n = 29) or ML (n = 27) received a unilateral intravitreal injection of scAAV8-hRs-IRBP at 21 days, and functional outcome was evaluated at 4 months by electroretinogram., Results: At 1 month, no functional or structural differences were found between LL- or ML-reared Rs1-KO mice. At 4 months, ML-reared Rs1-KO mice showed significant reduction of b-wave amplitude and b-/a-wave ratio with no changes in a-wave, and a significant increase in cavity size, compared to LL-reared animals. Moderate light rearing increased Kir4.1 expression in Rs1-KO mice by 4 months, but not AQP4 and GFAP levels. Administration of scAAV8-hRS1-IRBP to Rs1-KO mice showed similar improvement of inner retinal ERG function independent of LL or ML rearing., Conclusions: Rearing light conditions affect the development of retinal cavities and post-photoreceptor function in Rs1-KO mice. However, the effect of rearing light intensity does not interact with the efficacy of RS1 gene replacement in Rs1-KO mice.

Purpose: To assess macular microstructure in eyes with tilted disk syndrome (TDS) and determine the relationship between TDS foveal morphology and visual function., Methods: Twenty-six TDS eyes from 19 children (aged 5∼15 years) with a spherical equivalent refraction (SER) of -3.1 ± 1.3 diopter (D) and 28 control eyes from 14 children (aged 7∼12 years) with a SER of -3.0 ± 0.7 D were recruited. Horizontal and vertical optical coherence tomography scans through the fovea produced images that were segmented into eight intraretinal layers. Thicknesses of the total retina and each layer were measured at the foveal center and 12 other macular locations: 500 μm, 1,000 μm, and 1,500 μm along the horizontal and vertical meridians. The relationships between TDS best correct visual acuity (BCVA) and the presence of photoreceptor inner/outer segment (IS/OS) junction line, IS/OS foveal bulge, and cone outer segment tip (COST) line were evaluated., Results: The thickness of TDS central fovea, 218.94 ± 22.20 μm, was not significantly different from controls. The total retinal thickness in TDS eyes was thinner than controls at all peripheral locations (P < 0.05) except at 500 μm and 1,000 μm superiorly, and 1,500 μm temporally. Tilted disk syndrome intraretinal layer thicknesses in the nasal and inferior regions varied significantly from controls (P < 0.05). Only 80.7% and 23.1% of TDS eyes had a normal foveal bulge and continuous COST line, respectively, compared with 100% and 96.4% of controls. The BCVA of TDS eyes was similar whether or not the foveal bulge or COST line was abnormal., Conclusion: Differences in intraretinal layer thickness may be correlated with defective vision.

Purpose: To evaluate the role of serum urea and creatinine as surrogate markers for disruption of retinal photoreceptor external limiting membrane (ELM) and inner segment ellipsoid zone (EZ) in Type 2 diabetic retinopathy (DR) using spectral-domain optical coherence tomography, for the first time., Methods: One hundred and seventeen consecutive cases of Type 2 diabetes mellitus (diabetes without retinopathy [No DR; n = 39], nonproliferative diabetic retinopathy [NPDR; n = 39], proliferative diabetic retinopathy [PDR; n = 39]) and 40 healthy control subjects were included. Serum levels of urea and creatinine were assessed using standard protocol. Spectral-domain optical coherence tomography was used to grade the disruption of ELM and EZ as follows: Grade 0, no disruption of ELM and EZ; Grade 1, ELM disrupted, EZ intact; Grade 2, ELM and EZ disrupted. Data were analyzed statistically., Results: Increase in serum levels of urea (F = 22.93) and creatinine (F = 15.82) and increased grades of disruption of ELM and EZ (γ = 116.3) were observed with increased severity of DR (P < 0.001). Increase in serum levels of urea (F = 10.45) and creatinine (F = 6.89) was observed with increased grades of disruption of ELM and EZ (P = 0.001)., Conclusion: Serum levels of urea and creatinine are surrogate markers for disruption of retinal photoreceptor ELM and EZ on spectral-domain optical coherence tomography in DR.

Background: Intact foveal bulge has been associated with good visual outcome in retinal diseases. The aim of this study was to study the variation in foveal bulge with age., Methods: It was an observational cross-sectional study conducted between October 2014 and December 2015. Totally, 101 eyes of 101 healthy volunteers were studied in a tertiary care center. All individuals had best corrected visual acuity of 20/20 or better. High myopia (>6 D), high hyperopia (>4 D), unstable fixation, media opacities and retinal disorder like diabetic retinopathy, retinal vein occlusion were the exclusion criteria. Spectral domain optical coherence tomography was used to identify foveal bulge. The height of foveal bulge was measured as the distance between inner border of retinal pigment epithelium and outer border of inner segment - outer segment line (ellipsoid zone) at fovea. Main outcome measures were a correlation between the height of the foveal bulge and age of the participants., Results: Foveal bulge was present in 61 (60.4%) and absent in 40 (39.6%) eyes. Mean age of patients with and without foveal bulge was 33.3 ± 16.2 years and 44.1 ± 20.5 years respectively ( P = 0.02). Mean height of foveal bulge was 41.1 ± 6.4 μ (range: 23-51 μ). The height of the foveal bulge showed a negative correlation with the age of the participants ( r = -0.15)., Conclusion: Foveal bulge was more commonly seen in younger individuals and its height decreased with age. Age matching across groups should be undertaken in studies using foveal bulge as prognostic tool., Competing Interests: There are no conflicts of interest.

Purpose: We evaluate the expression of Gli1 in human epiretinal membranes (ERM) and correlate this with clinical data., Methods: We prospectively recruited patients with ERM. A total of 33 human ERM specimens were immunolabeled with anti-Gli1 antibody and the number of total cells/hyperfield (HF), Gli1(+) cells/HF, and the percentage of Gli1(+) cells/total cells were calculated. We evaluated the interrelationship of cellular properties and clinical findings, such as presence of diabetic retinopathy (DR), retinal breaks, intraocular inflammation, central foveal thickness, maximal retinal thickness, retinal contraction, lamellar holes, pseudoholes, the attenuation or absence of an inner segment/outer segment (IS/OS) junction/external limiting membrane (ELM), cystic changes, and paravascular inner retinal defects., Results: Among 33 specimens, 25 specimens (75.8%) showed nuclear Gli1 expression. The mean Gli1(+) cells/total cells was 54.0 ± 36.7% (range, 0%-92.8%). There was significantly higher expression of Gli1(+) cells in ERM specimens from patients with DR (P = 0.014), and lower expression from patients with retinal breaks (P = 0.022). Epiretinal membrane specimens from patients with alteration of IS/OS junction/ELM or cystic changes on OCT showed higher percentage of Gli1(+) cells/total cells., Conclusions: Gli1 expression was detected in most ERM specimens. Patients who had DR or OCT findings indicating chronic retinal insults showed higher Gli1 expression. Gli1 may have a role in the pathogenesis of ERM after chronic retinal insults.

Purpose: To compare optical coherence tomography (OCT) angiographic parameters in retina and choriocapillaris between control subjects and diabetic patients without diabetic retinopathy (NDR). Correlations were studied between OCT angiography parameters, retinal structure parameters, and systemic characteristics in all subjects., Methods: Sixty-two patients were included in the study: control subjects (n = 33) and patients with NDR (n = 29). Optical coherence topography angiographic parameters were as follows: vessel density (%) (in superficial, deep retinal vessel plexus and in choriocapillary layer) and foveal avascular zone (FAZ) area (mm2) in superficial and deep retinal vessel plexus of parafovea. Split-spectrum amplitude decorrelation angiography (SSADA) software algorithm was used for evaluation of vessel density and FAZ area (nonflow area tool). Spectral-domain OCT was used to assess full, inner, and outer retinal thickness and volume in parafovea., Results: In superficial and deep retina, vessel densities in NDR (44.35% ± 13.31% and 31.03% ± 16.33%) were decreased as compared to control subjects (51.39% ± 13.05%, P = 0.04; and 41.53% ± 14.08%, P < 0.01). Foveal avascular zone in superficial retina of NDR patients (0.37 ± 0.11 mm2) was greater than in controls (0.31 ± 0.10 mm2, P = 0.02). Superficial vessel density significantly correlated with full retinal thickness and volume in parafovea (r = 0.43, P = 0.01; r = 0.43, P = 0.01) and with outer retinal volume in parafovea (r = 0.35, P < 0.05) of healthy subjects. Systolic blood pressure and ocular perfusion pressure significantly correlated with deep vessel density in NDR (r = -0.45, P = 0.02; r = -0.46, P = 0.01), but not in controls., Conclusions: Superficial and deep retinal vessel density in parafovea of diabetic patients without diabetic retinopathy are both decreased compared to healthy subjects. The associations between vessel density with retinal tissue thickness and with subject's clinical characteristics differ between healthy subjects and patients with NDR.

Purpose: We improved our understanding of central serous chorioretinopathy (CSC), we performed an analysis of noninvasive, high-resolution retinal imaging in patients with active and resolved CSC., Methods: Adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography (SD-OCT) were performed on five subjects with CSC. A custom AOSLO system was used to simultaneously collect confocal and split-detector images. Spectral domain-OCT volume scans were used to create en face views of various retinal layers, which then were compared to montaged AOSLO images after coregistration., Results: Three distinct types of intraretinal hyperreflective clusters were seen with AOSLO. These clusters had a well-demarcated, round, and granular appearance. Clusters in active CSC over areas of serous retinal detachment were termed type-1. They were found primarily in the outer nuclear layer (ONL) and were associated with large defects in the photoreceptor mosaic and ellipsoid zone. Clusters in areas where the retina had reattached were termed type-2. They also were located primarily in the ONL but showed stability in location over a period of at least 8 months. Smaller clusters in the inner retina along retinal capillaries were termed type-3., Conclusions: Retinal imaging in CSC using en face OCT and AOSLO allows precise localization of intraretinal structures and detection of features that cannot be seen with SD-OCT alone. These findings may provide greater insight into the pathophysiology of the active and resolved phases of the disease, and support the hypothesis that intraretinal hyperreflective foci on OCT in CSC are cellular in nature.

Purpose: Choroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions., Methods: Twelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques., Results: Eleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina., Conclusions: Early IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors., Competing Interests: The authors have declared that no competing interests exist.

The neurotransmitter glutamate causes excitotoxicity in the human retina. In neonatal rats, the degree of glutamate-induced retinal damage depends on age at administration. To elucidate the sensitivity to glutamate on various developing stage of retina, we investigated glutamate-induced retinal damage and glutamate target cells on each postnatal day (PND). Newborn rats received a single subcutaneous administration of l-glutamate on PNDs 1 to 14. Retinal cell apoptosis characterized as pyknotic and terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling-positive nuclei was analyzed at 6 hr after treatment, and sequential morphological features of retina were evaluated on PND 21. The inner retina on PND 21 exhibited thinning in rats treated after PND 2. The thinning was most severe in rats treated on PND 8 and the number of apoptotic cells also peaked. No thinning was observed in rats treated on PND 14. In the inner nuclear layer, glutamate target cells were mainly amacrine cells; additionally, bipolar cells and horizontal cells were damaged on PND 8. These retinal changes were more severe in central retina than those in peripheral retina on PND 8. Our findings indicate the morphological consequences of glutamate-induced retinal excitotoxicity and glutamate target cells on each PND and reveal that glutamate-induced retinal damage depends on developing stage.

Purpose: To examine the integrity of the ellipsoid zone after perfluoro-n-octane use for reattachment of the central retina in macula-off retinal detachment cases., Methods: Intraoperative video documentation with microscope-integrated intraoperative spectral-domain optical coherence tomography (OCT) of 10 consecutive patients with macula-off retinal detachment, scheduled for primary vitrectomy for retinal detachment repair, was retrospectively examined for defects in the integrity of the ellipsoid zone due to perfluoro-n-octane use., Results: Successful intraoperative visualization was possible in all cases, retinal detachment was reattached in all cases, but residual islands of subretinal fluid persisted directly after perfluoro-n-octane use in 80% of cases. These were resorbed in all cases in the postoperative OCTs. Disturbances in the integrity of the ellipsoid zone or intraoperative macular hole formation did not present in any of our cases., Conclusions: Perfluoro-n-octane use seems to be a safe procedure regarding integrity of the ellipsoid zone in cases scheduled for primary vitrectomy for retinal detachment repair.

Purpose:: This study was conducted to evaluate the relationships of inner/outer segment (IS/OS) junction disruption, macular thickness, and epiretinal membrane (ERM) grade with best-corrected visual acuity (BCVA), as well as the relationship between IS/OS junction disruption and ERM grade., Methods:: Fifty-four eyes of 54 patients with different grades of ERM were retrospectively reviewed. Patients were classified into three groups by ERM grade according to retinal striae and vessel distortion: grade/group 1, visible membranes without retinal striae or vessel distortion; grade/group 2, mild to moderate macular striae or vessel straightening; and grade/group 3, moderate to severe striae and vascular straightening. Correlations of BCVA with age, central retinal thickness, ERM grade, and IS/OS disruption as well as of IS/OS disruption, central macular thickness, and BCVA with ERM grade were evaluated., Results:: Twenty-nine (53.7%) eyes exhibited IS/OS junction disruption. Groups 1 and 2 differed significantly with respect to BCVA (p=0.038), but groups 2 and 3 did not (p=0.070). Central macular thickness was significantly greater in group 2 than in group 1 (p=0.031) and in group 3 than in group 2 (p=0.033). Groups 1 and 2 differed significantly in terms of IS/OS disruption (p=0.000), but groups 2 and 3 did not (p=0.310)., Conclusions:: The IS/OS junction appears to be disrupted during the early stages of ERM. Grade 3 ERM is associated with a significantly higher incidence of IS/OS disruption.

Purpose: To investigate the correlation between the inner-retinal irregularity index and visual outcomes before and after idiopathic epiretinal membrane (ERM) surgery., Design: Retrospective cohort study., Methods: We analyzed 66 eyes of 66 patients with idiopathic ERM. Ophthalmic examinations included best-corrected visual acuity (BCVA) measurements, metamorphopsia assessment, and spectral-domain optical coherence tomography before surgery and 1, 3, and 6 months post-surgery. Correlations between the inner-retinal irregularity index, defined as the length ratio between the inner plexiform layer and retinal pigment epithelium, and visual outcomes before and after ERM surgery were evaluated and compared with the correlation between the central foveal thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness, interdigitation zone defect, and visual outcomes., Results: Inner-retinal irregularity index and central foveal thickness were significantly correlated with BCVA and metamorphopsia at each follow-up examination (all P < .05). The interdigitation zone defect correlated with BCVA at 3 and 6 months post-surgery (P < .001 and P < .015, respectively). However, GC-IPL thickness was not correlated with visual outcomes at any follow-up examination. The preoperative interdigitation zone defect was correlated with 6-month BCVA (P = .035) and the preoperative inner-retinal irregularity index was significantly correlated with the 6-month BCVA and marginally correlated with the 6-month metamorphopsia (P = .018 and P = .097, respectively)., Conclusion: The inner-retinal irregularity index was significantly correlated with visual outcomes before and after ERM surgery. This index can be used as a new surrogate marker for inner-retinal damage and a predictive prognostic marker in ERM., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To analyze inner retinal changes in patients with geographic atrophy (GA) secondary to age-related macular degeneration and identify morphological cues for progression., Methods: A total of 100 eyes with GA were assessed in this longitudinal, observational case series. Patients with GA and absent confounding pathology were compared with age-matched controls. The retinal layers on spectral-domain optical coherence tomography, acquired in tracking mode, were segmented manually on central scans through the fixation point. Zones of GA were defined based on choroidal signal enhancement from retinal pigment epithelium loss. An area of unaffected temporal retina was used for comparison. Progression of GA was quantified with fundus autofluorescence., Results: We analyzed 41 eyes of 41 patients (mean age 79.2 ± 6.7 years). In areas of GA, the layer representing the inner nuclear layer (INL) in healthy retina was increased in thickness. Thickness of this presumptive INL was inversely correlated with best-corrected visual acuity (r = -0.48, P < 0.01). The presumptive INL thickness increase in atrophic areas was less marked in eyes with foveal sparing. Increased INL thickness in areas adjacent to GA was associated with a higher progression rate., Conclusions: Optical coherence tomography findings demonstrate that atrophy of the retinal pigment epithelium-photoreceptor complex in GA is associated with an increase of thickness of the presumptive INL, presumably caused by remodeling of the degenerating retina. Similar alterations in the retina adjacent to areas clinically affected by GA were associated with higher atrophy progression rates.

Purpose: This article reports a method for en face optical coherence tomography (OCT) imaging and quantitative assessment of alterations in both thickness and reflectance of individual retinal layers at different stages of diabetic retinopathy (DR)., Methods: High-density OCT raster volume scans were acquired in 29 diabetic subjects divided into no DR (NDR) or non-proliferative DR (NPDR) groups and 22 control subjects (CNTL). A customized image segmentation method identified eight retinal layer interfaces and generated en face thickness maps and reflectance images for nerve fiber layer (NFL), ganglion cell and inner plexiform layers (GCLIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor outer segment layer (OSL), and retinal pigment epithelium (RPE). Mean thickness and intensity values were calculated in nine macular subfields for each retinal layer., Results: En face thickness maps and reflectance images of retinal layers in CNTL subjects corresponded to normal retinal anatomy. Total retinal thickness correlated negatively with age in nasal subfields (R ≤-0.31; P ≤ 0.03, N = 51). In NDR subjects, NFL and OPL thickness were decreased (P = 0.05), and ONL thickness was increased (P = 0.04) compared to CNTL. In NPDR subjects, GCLIPL thickness was increased in perifoveal subfields (P< 0.05) and INL intensity was higher in all macular subfields (P = 0.04) compared to CNTL., Conclusions: Depth and spatially resolved retinal thickness and reflectance measurements are potential biomarkers for assessment and monitoring of DR.

Purpose: To analyze the influence of spectral-domain optical coherence tomography (SD-OCT) features on visual acuity changes in patients with idiopathic epiretinal membranes (ERMs)., Methods: Seventy-nine eyes of 71 patients were included in this study. SD-OCT was performed for all patients; data were collected upon ERM diagnosis and at the final visit. The patients were divided into subgroups based on their SD-OCT features. The initial best corrected visual acuity (BCVA) and changes in BCVA for each subgroup were compared. A multivariate analysis was performed to assess the factors associated with changes in BCVA., Results: During a mean follow-up period of 20.78 months, the mean change in logMAR visual acuity was 0.052 ± 0.089. Eyes with inner segment/outer segment (IS/OS) junction disruption and cystoid macular edema (CME) had a significantly lower mean initial BCVA than those without disruption and CME (P = 0.036 and P = 0.012, respectively). However, only eyes with CME had significant changes in BCVA (P = .034). Multivariate analysis revealed the presence of CME as the only factor that had a significant correlation with VA changes., Conclusions: In patients with idiopathic ERMs, the presence of CME and IS/OS disruption detected by OCT correlated with a poorer initial BCVA. Most patients' visual acuity remained stable during follow-up. The presence of CME with OCT represented a predictor of the progression of visual acuity. These results may provide valuable clinical information regarding the management of patients with idiopathic ERMs. We demonstrated that the presence of CME and IS/OS disruption detected with OCT correlated with a poorer BCVA in idiopathic ERMs. The visual acuity of most patients was stable during the follow-up period. The presence of CME in OCT represented a predictor of vision deterioration for patients with idiopathic ERMs.

PurposeTo describe the intraretinal microstructure using serial spectral domain optical coherence tomography (SD-OCT) preceding and following pars plana vitrectomy and delamination of fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR).MethodsThis retrospective, interventional case series includes 28 eyes. Outcome measures included LogMAR distance best-corrected visual acuity (BCVA), SD-OCT integrity of photoreceptor inner and outer segments junction (IS/OS), and integrity of external limiting membrane (ELM).ResultsPre-operative central macular thickness (CMT) was significantly correlated with the final post-operative LogMAR BCVA (Pearson's coefficient r=0.89; P=0.001). The eyes were categorised into three groups based on post-operative IS/OS integrity (group 0: IS/OS intact; group 1: IS/OS irregular but not completely disrupted; group 2: IS/OS completely disrupted). Mean BCVA improved significantly in group 0 (n=9) from 1.13±0.75 preoperatively to 0.34±0.21 (Student's t-test: P=0.06), in group 1 (n=10) the BCVA improved from 0.88±0.56 to 0.58±0.31 (Student's t-test: P=0.053) and in group 2 (n=9) the BCVA improved from 1.64±0.53 to 1.53±0.75 (Student's t-test: P=0.652).IS/OS integrity and ELM integrity at 3 months post operatively, were significantly and positively correlated with final BCVA (Pearson's coefficient: r=0.83, P<0.001 and r=0.72, P<0.001, respectively).ConclusionsPre-operative CMT and post-operative disruption of the IS/OS and ELM are useful prognostic indicators in fibrovascular delamination surgery for patients with PDR.

Optical Coherence Tomography (OCT) is a powerful clinical tool that measures near infrared light backscattered from the eye and other tissues. OCT is used for assessing changes in retinal structure, including layer thicknesses, detachments and the presence of drusen in patient populations. Our custom-built OCT system for the mouse eye quantitatively images all layers of the neural retinal, the RPE, Bruchs' membrane and the choroid. Longitudinal assessment of the same retinal region reveals that the relative intensities of retinal layers are highly stable in healthy tissue, but show progressive increases in intensity in a model of retinal degeneration. The observed changes in OCT signal have been correlated with ultrastructural disruptions that were most dramatic in the inner segments and nuclei of the rods. These early changes in photoreceptor structure coincided with activation of retinal microglia, which migrated vertically from the inner to the outer retina to phagocytose photoreceptor cell bodies (Levine et al., Vis Res 102:71-79, 2014). We conclude that quantitative analysis of OCT light scattering signals may be a useful tool for early detection and subcellular localization of cell stress prior to cell death, and for assessing the progression of degenerative disease over time. Future efforts to develop sensitive approaches for monitoring microglial dynamics in vivo may likewise elucidate earlier signs of cellular stress during retinal degeneration.

Retinal degeneration (RD) such as retinitis pigmentosa and age-related macular degeneration are major causes of blindness in adulthood. As one of the model for RD, intraperitoneal injection of N-methyl-N-nitrosourea (MNU) is widely used because of its selective photoreceptor cell death. It has been reported that MNU increases intracellular calcium ions in the retina and induces photoreceptor cell death. Although calcium ion influx triggers the neuronal nitric oxide synthase (nNOS) activation, the role of nNOS on photoreceptor cell death by MNU has not been reported yet. In this study, we investigated the contribution of nNOS on photoreceptor cell death induced by MNU in mice. MNU significantly increased NOS activation at 3 day after treatment. Then, we evaluated the effect of nNOS specific inhibitor, ethyl[4-(trifluoromethyl) phenyl]carbamimidothioate (ETPI) on the MNU-induced photoreceptor cell death. At 3 days, ETPI clearly inhibited the MNU-induced cell death in the ONL. These data indicate that nNOS is a key molecule for pathogenesis of MNU-induced photoreceptor cell death.