Superior Retina Research Articles

Retinal pathological features and proteome signatures of Alzheimer’s disease

Alzheimer’s disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors. Quantitative examination of superior and inferior temporal retinas from mild cognitive impairment (MCI) and AD patients compared to those with normal cognition (NC) revealed significant increases in amyloid β-protein (Aβ42) forms and novel intraneuronal Aβ oligomers (AβOi), which were closely associated with exacerbated retinal macrogliosis, microgliosis, and tissue atrophy. These pathologies were unevenly distributed across retinal layers and geometrical areas, with the inner layers and peripheral subregions exhibiting most pronounced accumulations in the MCI and AD versus NC retinas. While microgliosis was increased in the retina of these patients, the proportion of microglial cells engaging in Aβ uptake was reduced. Female AD patients exhibited higher levels of retinal microgliosis than males. Notably, retinal Aβ42, S100 calcium-binding protein B+ macrogliosis, and atrophy correlated with severity of brain Aβ pathology, tauopathy, and atrophy, and most retinal pathologies reflected Braak staging. All retinal biomarkers correlated with the cognitive scores, with retinal Aβ42, far-peripheral AβOi and microgliosis displaying the strongest correlations. Proteomic analysis of AD retinas revealed activation of specific inflammatory and neurodegenerative processes and inhibition of oxidative phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps retinopathy in MCI and AD patients, demonstrating the quantitative relationship with brain pathology and cognition, and may lead to reliable retinal biomarkers for noninvasive retinal screening and monitoring of AD.

Early onset of age-related changes in the retina of cystine/glutamate antiporter knockout mice

To determine the role of the cystine/glutamate antiporter on retinal structure and function, retinas of C57Bl/6J wild-type and xCT knockout mice, lacking the xCT subunit of the cystine/glutamate antiporter were examined from 6 weeks to 12 months of age. Fundoscopy, optical coherence tomography (OCT), and whole mount retinal autofluorescence imaging were used to visualise age-related retinal spots. Glial fibrillary acidic protein (GFAP) immunolabelling was used to assess retinal stress. Retinal function was evaluated using full-field and focal electroretinograms. Examinations revealed retinal spots in both wild-type and xCT knockout mice with the number of spots greater at 9 months in the knockout compared to wild-type. OCT confirmed these discrete spots were located at the retinal pigment epithelium (RPE)–photoreceptor junction and did not label with drusen markers. Whole mount lambda scans of the 9 month xCT knockout retinas revealed that the photoreceptor autofluorescence matched the spots, suggesting these spots were retinal debris. GFAP labelling was increased in knockout retinas compared to wild-type indicative of retinal stress, and the discrete spots were associated with migration of microglia/macrophages to the RPE-retina intersection. OCT revealed that the superior retina was thinner at 9 months in knockout compared to wild-type mice due to changes to the outer nuclear and photoreceptor layers. While global retinal function was not affected by loss of xCT, focal changes in retinal function were detected in areas where spots were present. Tother these results suggest that the xCT KO mice exhibit features of accelerated ageing and suggests that this mouse model may be useful for studying the underlying cellular pathways in retinal ageing.

Recurrent vitreous opacity caused by intraocular Toxocara larva: a case report and literature review

BackgroundToxocara larva entity has seldom been reported on the surface of the retina. We report on an unusual case of recurrent vitreous opacity caused by intraocular Toxocara larva after vitrectomy.Case presentationA 34-year-old male was referred to our clinic with a 6-month history of decreased visual acuity in the right eye characterized as red, painless, and progressive. Optos fundus photograph showed optic disc elevation with granuloma, and proliferative membrane starting from the optic disc and running towards the superior temporal retina due to the movement of a Toxocara larva, which was covered by the proliferative membrane in the superior temporal retina. Since it adhered closely to the retina, the lesion in the superior temporal retina was not removed to avoid induction of an iatrogenic retinal break and the larva was not found during the first diagnostic pars plana vitrectomy. Intraocular Anti-Toxocara IgG was 45.53U (< 3, enzyme-linked immunosorbent assay (ELISA)), and the Goldmann-Witmer coefficient was 8.55, confirming the diagnosis of ocular toxocariasis. After this operation, visual acuity improved to 20/200. However, vitreous opacity worsened again, and the proliferative membrane expanded around the Toxocara larva three weeks after the operation. Toxocara larva was found and removed in the superior temporal region during the second operation. His visual acuity improved to 20/100, vitreous opacity disappeared, and the retina was stable two months after the second operation.ConclusionIt is advisable to remove suspected Toxocara larva to prevent the reoccurrence of ocular toxocariasis.

Retinal Shape-Based Classification of Retinal Detachment and Posterior Vitreous Detachment Eyes.

Retinal detachment is a sight-threatening emergency, with more than half of those affected suffering permanent visual impairment. A diagnostic test to identify eyes at risk before vision is threatened would enable exploration of prophylactic treatment. This report presents the use of irregularities in retinal shape, quantified from optical coherence tomography (OCT) images, as a biomarker for retinal detachment. OCT images were taken from posterior and mid-peripheral retina of 264 individuals [97 after a posterior vitreous detachment (PVD), 99 after vitrectomy for retinal detachment and 68 after laser for a retinal tear]. Diagnoses were taken from history, examination and OCT. Retinal irregularity was quantified in the frequency domain, and the distribution of irregularity across the regions of the eye was explored to identify features exhibiting the greatest difference between retinal detachment and PVD eyes. Two of these features plus axial length were used to train a quadratic discriminant analysis classifier. Classifier performance was assessed by its sensitivity and specificity in identifying retinal detachment eyes and visualised with a receiver operating characteristic (ROC) curve. Validation set specificity was 84% (44/52 PVD eyes correctly labelled) and sensitivity 35% (23/64 retinal detachment eyes identified, p = 0.02). Area under the ROC curve was 0.75 (95% confidence intervals 0.58-0.85). Retinal detachment eyes were significantly more irregular than PVD eyes in the superior retina (0.70mm versus 0.49mm, p < 0.05) and supero-temporal retina (1.12mm versus 0.80mm, p < 0.05). Lower sensitivity (16/68, 24%) was seen for eyes with a retinal tear without detachment, that were intermediate in size between retinal detachment and PVD eyes. Axial length on its own was a poor classifier. Neither irregularity nor classification were affected by surgery for retinal detachment or the development of PVD. The classifier identified 1/3 of retinal detachment eyes in this sample. In future work, these features can be evaluated as a test for retinal detachment prior to PVD.

CMV retinitis and subsequent acute cystoid macular oedema after treatment with vitreous ganciclovir injection: a case report

BackgroundTo report a very rare acute cystoid macular oedema following ganciclovir injection in patients receiving allogeneic haematopoietic stem cell transplantation.Case presentationA 44-year-old male patient experienced vision loss in his left eye eight months after allogeneic stem cell transplantation. Ophthalmologic examination showed posterior retinopathy with retinal haemorrhage, a yellow necrotic border, and a vascular white sheath involved in the superior temporal retina but not the posterior pole. Cytomegalovirus DNA results in both plasma and ocular fluid were positive. All tests combined with the patient’s medical history suggested that his ocular disease was cytomegalovirus retinitis. Consequently, he received a weekly ganciclovir vitreous injection. The disease was visibly controlled, and the fundus condition improved after the first three treatments. However, the patient had severe vision loss in his left eye and acute cystic oedema in the macula, while the original lesion was stable two hours after the fourth treatment. The macular oedema subsided significantly on the first day. Over the next week, daily OCT findings indicated that the patient's macular oedema gradually subsided and resolved completely by the second week, and his left eye vision partially improved.ConclusionMacular oedema may occur in patients with cytomegalovirus retinitis, but it rarely occurs during treatment. In this case, the patient's macular oedema appeared and resolved quickly. Macular oedema in patients with cytomegalovirus retinitis receiving vitreous cavity injections of ganciclovir needs to be further studied and discussed.

Baseline retinal vascular bed area on ultra-wide field fluorescein angiography correlates with the anatomical outcome of diabetic macular oedema to ranibizumab therapy: two-year analysis of the DAVE Study.

To determine the relationship between baseline retinal non-perfusion area (NPA) and retinal vascular bed area (RVBA) on ultra-wide field fluorescein angiography (UWF FA) and long-term response to intravitreal ranibizumab therapy in diabetic macular oedema (DMO). A post-hoc, 2-year observational case series. Baseline UWF FA images (Optos 200Tx) of 40 eyes from 29 patients with diabetes mellitus and treatment naïve DMO in the DAVE (NCT01552408) study were montaged and stereographically projected at the Doheny Image Reading Center to adjust for peripheral distortion. The retinal vasculature was automatically extracted to calculate RVBA. NPA was manually delineated by two masked certified graders. RVBA and NPA were computed in mm2 automatically by adjusting for peripheral distortion and then correlated with the severity of DMO. While global NPA at baseline was not correlated to retinal thickness measurements, baseline NPA in the superior retina was associated with the macular volume (MV) improvement (P = 0.022). Multivariate analysis revealed a smaller RVBA at baseline was correlated with a better MV outcome at two-year follow-up after adjusting for confounding factors (P = 0.049). Eyes with smaller baseline RVBA appear to have a better long-term anatomic outcome of DMO.

A case of branch retinal vein and artery occlusion following intranasal cocaine abuse

The known ocular effects of cocaine abuse include nystagmus and retinal vascular occlusions, among others. Retinal vascular occlusions are rarely seen in young adults and are thus generally associated with hypercoagulable disorders. Increasing rates of cocaine abuse in Western countries have led to increased reports of vascular complications. In addition to common vascular complications of myocardial infarction and stroke, cocaine-induced vasospasm can manifest in visual impairment. Previously, only two case reports of central retinal artery occlusion have been reported in intranasal cocaine abusers. This case report details combined branch retinal artery occlusion and branch retinal vein occlusion in one eye of an intranasal cocaine abuser. A 40-year-old man presented to our clinic with sudden painless nasal field loss of his left eye. The patient reported a recent history of intranasal cocaine use. Fundus examination showed intraretinal hemorrhage in the superior papillary, superior retina, temporal macula, and retinal thickening. We present a case of a patient with unilateral branch retinal vein and artery occlusions, possibly associated with induction of vascular spasm following cocaine abuse.

Effect of Accommodation on Peripheral Higher Order Aberrations

Knowledge of the effect of accommodation on image quality of peripheral retina is crucial for better understanding of the visual system, but only a few studies have been carried out in this area. This study was designed to evaluate the effect of accommodation on higher order aberrations from third to sixth Zernike polynomials in central and peripheral retina up to 23° off-axis. We used a Hartmann–Shack aberrometer to measure Zernike coefficients with both accommodated and non-accommodated eyes of 15 healthy subjects. Each Zernike coefficient, total higher order aberrations, spherical aberrations and astigmatism were compared between accommodated and non-accommodated status. Additionally, aberrations in the central retina were compared with the peripheral retina. Accommodation induced significant changes in the Zernike coefficients of vertical pentafoil C5−5 and secondary vertical tetrafoil C6−4 in central retina, secondary vertical astigmatism C4−2 on 23° of temporal retina, secondary vertical tetrafoil C6−4 and tertiary vertical astigmatism C6−2 on 10° of nasal retina, secondary vertical trefoil C5−3 and secondary vertical tetrafoil C6−4 on 23° of nasal retina, and horizontal tetrafoil C44, and secondary horizontal tetrafoil C64 on 23° of inferior retina (p &lt; 0.05). Total higher order aberration was lower in each retinal area examined with accommodation, but it was statistically significant only on 23° temporal retina and 11.5° and 23° of superior retina (p &lt; 0.05). Spherical aberration decreased with accommodation on 23° temporal retina (p = 0.036). Astigmatism was similar in non-accommodated and accommodated eyes. Overall, accommodation affected higher order aberration (HOA) asymmetrically in different peripheral retinal areas.

Trilogy Development of Proopiomelanocortin Neurons From Embryonic to Adult Stages in the Mice Retina.

Proopiomelanocortin-positive amacrine cells (POMC ACs) were first discovered in adult mouse retinas in 2010; however, the development of POMC-ACs has not been studied. We bred POMC-EGFP mice to label POMC-positive cells and investigated the development of POMC neurons from embryonic to adult stages. We found that POMC neuron development is mainly divided into three stages: the embryonic stage, the closed-eye stage, and the open-eye stage. Each stage has unique characteristics. In the embryonic stage, POMC neurons appeared in the retina at about E13. There was a cell number developmental peak at E15, followed by a steep decline at E16. POMC neurons showed a large soma and increased spine numbers at the closed-eye stage, and two dendritic sublaminas formed in the inner plexiform layer (IPL). The appearance and increased soma size and dendrite numbers did not occur continuously in space. We found that the soma number was asymmetric between the superior and inferior retinas according to the developmental topographic map. Density peaked in the superior retina, which existed persistently in the retinal ganglion cell layer (GCL), but disappeared from the inner nuclear layer (INL) at about P6. At the same time, the soma distribution in the INL was the most regular. At the open-eye stage, the development of POMC neurons was nearly stable only with only an increase in the IPL width, which increased the soma–dendrite distance.

Computational Fluid Dynamics of Intraocular Silicone Oil Tamponade.

PurposeTo investigate the behavior of silicone oil (SiO) at the steady equilibrium and during saccades and calculate SiO-retina contact, shear stress (SS), and shear rate (SR).MethodsA 24 mm phakic eye mesh model underwent 50°/0.137s saccade. The vitreous chamber compartment was divided into superior and inferior 180° sectors: lens, pre-equator, postequator, and macula. SiO-retina contact was evaluated as a function of fill percentages between 80% and 90% for a standing patient, 45° upward gaze, and supine. SS and SR for 1000 mPa-s (SiO1000) and 5000 mPa-s (SiO5000) silicon oil were calculated.ResultsSiO fill between 80% to 90% allowed 55% to 78% retinal contact. The superior retina always kept better contact with SiO, regardless of the fill percentage (P < 0.01). SiO interface thoroughly contacted the macula only in standing position. SS followed a bimodal behavior and was always significantly higher for SiO5000 compared to SiO1000 (P < 0.01) throughout the saccade. The macula suffered the highest mean SS in standing position, while throughout the saccade the average SS was maximum at the SiO-aqueous interface. SR was significantly higher for SiO1000 compared to SiO5000 (P < 0.001).ConclusionsSS on the retinal surface may instantaneously exceed reported retinal adhesiveness values especially at the SiO-aqueous interface and possibly favor redetachment. Despite 90% SiO fill the inferior retina remains extremely difficult to tamponade.Translational RelevanceAccurate assessment of retina-tamponade interaction may explain recurrent inferior retinal redetachment, silicone oil emulsification, and help to develop better vitreous substitutes.

Association of inner retinal reflectivity with qualitative and quantitative changes in retinal layers over time in diabetic eyes without retinopathy.

To assess the course of neurodegeneration based on retinal layer thickness and integrity analysis in diabetic patients without retinopathy and to evaluate its association with inner retinal reflectivity. This retrospective case-control study included 80 eyes of 80 patients with DM without retinopathy and 40 eyes of 40 healthy subjects with a follow-up of ≥1 year. SD-OCT was used for assessment of retinal reflectivity and macular layer thicknesses. Optical intensity ratios (OIRs) were defined as the mean OCT reflectivity of ganglion cell and inner nuclear layer to the mean reflectivity of RPE. After Bonferroni correction, thinning in pericentral, superior and nasal sectors in total retina, superior ganglion cell, pericentral and nasal inner plexiform, and superior inner retinal layers, as well as thickening in inferior and pericentral outer plexiform layer remained significant in the study group (p < 0.0125). Ganglion cell layer OIR significantly correlated with the changes in superior retina (r = 0.278, p = 0.013), central inner retina (r = 0.247, p = 0.027), and pericentral retinal thickness (r = 0.240, p = 0.032), and no eyes had disruption of retinal layers in the study group initially or finally. Ganglion cell layer reflectivity significantly correlated with the amount of pericentral retinal thinning during the time course in the diabetic group, which was more prominent in the inner retinal layers.

Correcting QUEST Magnetic Resonance Imaging-Sensitive Free Radical Production in the Outer Retina In Vivo Does Not Correct Reduced Visual Performance in 24-Month-Old C57BL/6J Mice.

PurposeTo test the hypothesis that acutely correcting a sustained presence of outer retina free radicals measured in vivo in 24-month-old mice corrects their reduced visual performance.MethodsMale C57BL/6J mice two and 24 months old were noninvasively evaluated for unremitted production of paramagnetic free radicals based on whether 1/T1 in retinal laminae are reduced after acute antioxidant administration (QUEnch-assiSTed [QUEST] magnetic resonance imaging [MRI]). Superoxide production was measured in freshly excised retina (lucigenin assay). Combining acute antioxidant administration with optical coherence tomography (i.e., QUEST OCT) tested for excessive free radical–induced shrinkage of the subretinal space volume. Combining antioxidant administration with optokinetic tracking tested for a contribution of uncontrolled free radical production to cone-based visual performance declines.ResultsAt two months, antioxidants had no effect on 1/T1 in vivo in any retinal layer. At 24 months, antioxidants reduced 1/T1 only in superior outer retina. No age-related change in retinal superoxide production was measured ex vivo, suggesting that free radical species other than superoxide contributed to the positive QUEST MRI signal at 24 months. Also, subretinal space volume did not show evidence for age-related shrinkage and was unresponsive to antioxidants. Finally, visual performance declined with age and was not restored by antioxidants that were effective per QUEST MRI.ConclusionsAn ongoing uncontrolled production of outer retina free radicals as measured in vivo in 24 mo C57BL/6J mice appears to be insufficient to explain reductions in visual performance.

Evaluation of outer nuclear layer overshadowed by retinal vessels in retinitis pigmentosa.

We investigated in vivo light-induced photoreceptor damage in retinitis pigmentosa (RP) using spectral-domain optical coherence tomography (SD-OCT) images. We retrospectively reviewed patients with genetic diagnosis of EYS-associated RP. The outer nuclear layer (ONL) thickness under retinal vessels was measured on SD-OCT vertical scans. As a control, we measured adjacent ONL thickness 100 μm superior and inferior from the vessel. Same measurements were performed in healthy subjects. We calculated the ratio of ONL thickness under vessel divided by the average of adjacent ONL thickness and defined as ONL preservation ratio. In patients with RP, the length of ellipsoid zone (EZ) from the fovea was also measured with SD-OCT vertical scans. Thirty EYS-associated RP patients and 25 healthy subjects were included. In both groups, ONL thickness overshadowed by retinal vessels was not significantly different from that of adjacent area. However, ONL preservation ratio of RP was larger than that of healthy control in both superior and inferior retina (1.03 vs 0.97; p < 0.01, 1.15 vs 0.95; p < 0.01, respectively). In RP, ONL preservation ratio was significantly larger in the inferior retina than superior retina (p < 0.01). Furthermore, in RP patients, the EZ length from the fovea was always shorter in the inferior than superior retina and there was a significant difference (p < 0.01). Patients with EYS-associated RP exhibited inferior-dominant photoreceptor death and the relative ONL preservation under retinal vessels. These results suggest that longitudinal environment light exposure may be correlated with the photoreceptor death.

Relative light sensitivities of four retinal hemi-fields for suppressing the synthesis of melatonin at night

The magnitude of the stimulus to the biological clock will depend upon the distribution of circadian phototransduction circuits across the retinae and the spatial distribution of luminous stimuli in the environment. The present study compared nocturnal melatonin suppression for light exposures to the superior, inferior, nasal, and temporal retina in one eye independent of shading from the brow and the nose. The stimulus was a 40° diameter luminous disc, half of which was blue light (LED, λpeak = 470 nm) and the other amber light (LED, λpeak = 590 nm). Experimentally, the orientation of the bipartite disc was rotated to each of the four cardinal points of the visual field. A full, 40° blue disc was also employed by replacing the amber half-disc with another blue half-disc. The blue full- and half-discs always produced 100 photopic lx at the cornea. As hypothesized, nocturnal melatonin suppression was statistically greatest when the blue half-disc was delivered to the nasal hemi-field (35%); the other three hemi-fields were equally affected by the blue half-disc (≈20%). Melatonin suppression for the full-disc was 24%, which was not statistically different than the average suppression for the four hemi-fields of 27%.

Sildenafil-evoked photoreceptor oxidative stress in vivo is unrelated to impaired visual performance in mice.

PurposeThe phosphodiesterase inhibitor sildenafil is a promising treatment for neurodegenerative disease, but it can cause oxidative stress in photoreceptors ex vivo and degrade visual performance in humans. Here, we test the hypotheses that in wildtype mice sildenafil causes i) wide-spread photoreceptor oxidative stress in vivo that is linked with ii) impaired vision.MethodsIn dark or light-adapted C57BL/6 mice ± sildenafil treatment, the presence of oxidative stress was evaluated in retina laminae in vivo by QUEnch-assiSTed (QUEST) magnetic resonance imaging, in the subretinal space in vivo by QUEST optical coherence tomography, and in freshly excised retina by a dichlorofluorescein assay. Visual performance indices were also evaluated by QUEST optokinetic tracking.ResultsIn light-adapted mice, 1 hr post-sildenafil administration, oxidative stress was most evident in the superior peripheral outer retina on both in vivo and ex vivo examinations; little evidence was noted for central retina oxidative stress in vivo and ex vivo. In dark-adapted mice 1 hr after sildenafil, no evidence for outer retina oxidative stress was found in vivo. Evidence for sildenafil-induced central retina rod cGMP accumulation was suggested as a panretinally thinner, dark-like subretinal space thickness in light-adapted mice at 1 hr but not 5 hr post-sildenafil. Cone-based visual performance was impaired by 5 hr post-sildenafil and not corrected with anti-oxidants; vision was normal at 1 hr and 24 hr post-sildenafil.ConclusionsThe sildenafil-induced spatiotemporal pattern of oxidative stress in photoreceptors dominated by rods was unrelated to impairment of cone-based visual performance in wildtype mice.

Computational fluid dynamics (CFD) simulation analysis on retinal gas cover rates using computational eye models

We investigated the change in the retinal gas cover rates due to intraocular gas volume and positions using computational eye models and demonstrated the appropriate position after pars plana vitrectomy (PPV) with gas tamponade for rhegmatogenous retinal detachments (RRDs). Computational fluid dynamic (CFD) software was used to calculate the retinal wall wettability of a computational pseudophakic eye models using fluid analysis. The model utilized different gas volumes from 10 to 90%, in increments of 10% to the vitreous cavity in the supine, sitting, lateral, prone with closed eyes, and prone positions. Then, the gas cover rates of the retina were measured in each quadrant. When breaks are limited to the inferior retina anterior to the equator or multiple breaks are observed in two or more quadrants anterior to the equator, supine position maintained 100% gas cover rates in all breaks for the longest duration compared with other positions. When breaks are limited to either superior, nasal, or temporal retina, sitting, lower temporal, and lower nasal position were maintained at 100% gas cover rates for the longest duration, respectively. Our results may contribute to better surgical outcomes of RRDs and a reduction in the duration of the postoperative prone position.

Visual function in guinea pigs: behavior and electrophysiology

ABSTRACT Clinical relevance Guinea pig visual function is characterised based on behavioural and electrophysiological measures and retinal ganglion cell density is examined to further develop the guinea pig as a model of human ocular conditions. Background Guinea pigs are an important model of human ocular conditions. Here, guinea pig spatial frequency discrimination, pattern and full-field photopic electroretinography (ERG), and retinal ganglion cell distribution were investigated. Methods Adult guinea pigs (n = 6) were included. Optomotor responses to square-wave gratings from 0.3 to 2.4 cycles per degree (cpd) were assessed. Pattern ERG responses were recorded using square-wave gratings from 0.025 to 0.25 cpd at 100% contrast, alternating at a temporal frequency of 1.05 Hz. Full-field ERG responses were recorded using a 10.0 cd.s/m2 flash. Ganglion cell density was determined histologically from retinal whole mounts. Results Maximum spatial frequency discrimination was 1.65 ± 0.49 cpd for stimuli rotating temporally to nasally and 0.75 ± 0.16 cpd for stimuli rotating nasally to temporally. For pattern ERG, a maximum amplitude of 3.50 ± 1.16 µV for the first negative to positive peak (N1P1) was elicited with a 0.025 cpd grating, and 2.5 ± 0.1 µV for the positive to second negative peak (P1N2) was elicited with a 0.05 cpd grating. For full-field ERG, a-wave amplitude was 19.2 ± 4.24 µV, b-wave amplitude was 33.6 ± 8.22 µV, and the PhNR was 24.0 ± 5.72 µV. Peak retinal ganglion cell density was 1621 ± 129 cells/mm2, located 1–2 mm superior to the optic nerve head. Conclusion Guinea pigs show directional selectivity for stimuli moving in the temporal to the nasal visual field. Guinea pigs demonstrate a quantifiable PhNR in the full-field ERG and negative and positive waveforms in the pattern ERG. The visual streak is located in the superior retina.

Decreased Retinal Vascular Density in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI): An Optical Coherence Tomography Angiography (OCTA) Study.

BackgroundTo explore the retinal vascular density changes in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) patients using optical coherence tomography angiography (OCTA).MethodsWe recruit 62 AD patients, 47 MCI patients, and 49 cognitively healthy controls (HC) in this study. All participants in the study received a comprehensive ophthalmological and neurological evaluation, including global cognitive screening, as well as the Mini-Mental State Examination (MMSE), and completed the following eye examinations: visual acuity (VA), intraocular pressure (IOP), examination with slit-lamp, fundus photography (Version 1.5.0.0, NIDEK CO, LTD) and Optical coherence tomography imaging (software ReVue version 2017.1.0.155, Optovue Inc., Fremont, CA, United States). The visual rating scales for atrophy and white matter lesion in MRI was evaluated for all the patients with AD and MCI.ResultsIn the AD patient group, the superficial vascular density in the superior, inferior and whole retina was 44.64 ± 3.34, 44.65 ± 3.55, and 44.66 ± 3.36, respectively. These values were 44.24 ± 3.15, 43.72 ± 3.16, and 44 ± 3.07, respectively, in the MCI patient group. After multivariate analysis of the generalized linear model, adjustments for the confounding factors of sex, age, hypertension, diabetes and the quality index of OCTA image, the superficial vascular density in the AD and MCI patient groups was significantly lower than that in the HC group (P < 0.05): 46.94 ± 2.04, 46.67 ± 2.26, and 46.82 ± 2.08, respectively. No difference in the area of the FAZ among the three groups was observed (AD group: 0.34 ± 0.11 mm2; MCI group: 0.36 ± 0.12 mm2; control group: 0.33 ± 0.12 mm2, p > 0.05). The ganglion cell complex (GCC) thickness, inner parafovea thickness, and peripapillary retinal nerve fiber layer (p-RNFL) thickness were associated with the superficial vascular density. We found no significant correlation between the global cognition (MMSE scores) or between the Fazekas score and retinal OCT angiogram flow density.ConclusionThe superficial vascular density in the AD and MCI patient groups was significantly lower than that in the HC group. Our findings suggest the retinal microvascular dysfunction occurred in MCI and AD.

A case of choroidal osteoma

PurposeChoroidal osteoma is a benign ossifying tumor of unknown etiology, is characterized by a slightly irregular elevated yellow–white lesion that typically occurs in healthy females in their early twenties or thirties. Associated complications include choroidal neovascularization (CNV) and subretinal hemorrhage. To date, no associations have been reported with ocular or systemic diseases; however, some reports suggest links with Stargard's and polypoidal maculopathies.Methods17‐year‐old female was referred for complaints of blurring and decreased vision in the right eye who was diagnosed with choroidal neovascularization (CNV) associated with choroidal osteoma.ResultsWe report the case of a 17‐year‐old female who presented to the hospital with complaints of blurring and decreased vision and loss of part of temporal visual field in the right eye. The patient had no systemic disease or family history of retinal lesions. Her visual acuity was 20/125 and 20/20 in the right and left eyes, respectively. Fundus examination of the right eye revealed a subretinal orange 4 × 3 disc diameter lesion with irregular distinct margins located in the superior retina with partial macular involvement. B‐scan indicated an echodense lesion sized 7.2 mm × 8.3 mm × 1.1 mm, with thick choroidal hemorrhage, strong shadowing, and subretinal calcification next to the optic disc. angiography showed dye leakage in the foveal region (CNV) and dye staining in an area of chronic retinal pigment epithelium (RPE) decompensation overlying the lesion. OCT indicated hyperreflectivity and subretinal fluid. Unilateral choroidal osteoma with secondary CNV was confirmed. The patient received intravitreal anti‐VEGF injection every 2 months. OCT was performed at each visit, indicating subretinal fluid. After 6 months, the clinical examination indicated a dry macular that was confirmed with OCT. There was functional improvement and anti‐VEGF injection continued for a total of seven injections over a period of almost 14 months. At the last visit, FFA indicated a stable dry macula, no CNV. The lesion size and vision were stable. The patient remains under observation.ConclusionsLong‐term follow‐up is necessary to resolve the fluids, possible development of CNV, and possible of bilateral occurrence.

Retinal thickness changes over time in a AD mouse model (APPNL‐F/NL‐F) by SD‐OCT

PurposeAlzheimer' disease (AD) is a neurodegenerative brain pathology, characterized by a loss of neuron and their synapses. Similar changes have been found in the retina even before appeared in the brain. The retina has been postulated as an accessible biomarker of AD. The aim of this study was to analyze changes in retinal thickness over time in a mouse model of AD (APPNL‐F/NL‐F).MethodsRetinas of male APPNL‐F/NL‐F (n = 55) and WT (n = 39) animals were evaluated in vivo by SD‐OCT at 6, 9, 12, 15, 17 and 20 months old. The mean total retinal thickness was analysed following the ETDRS sectors. To analyse the RNFL, axonal ring scan around the optic nerve head was carried out. RNFL was measured in six sectors provided by the manufacturer. Only the left eyes were used to study.ResultsIn the APPNL‐F/NL‐F group compared to WT animals, the total retinal thickness showed a slight thinning up to the 15 months old, this being significant only at 6 months in the outer temporal ring. At 17 months, there was thickening in the total retinal thickness being significant in the inferior and nasal sectors, both in inner and outer rings. At 20 months, there was a significant thinning in superior and temporal retina, both in inner and outer rings. RNFL thickness showed similar changes, that being only significates, the thinning in the global analysis and in nasal and inner‐temporal sectors at 6 months old.ConclusionsIn the mouse model of AD (APPNL‐F/NL‐F), there is a thinning of the retinal thickness up to 15 months, followed by a thickening at 17 months and a subsequent thinning at 20 months in some retinal areas. These changes over time are similar to those observed in the human retina, with areas of thinning, possibly caused by neurodegeneration, followed by thickening, possibly caused by deposits and neuroinflammation; this experimental AD model could help for an extensive understanding of the different retinal changes during the AD progression.