Changes In Inner Nuclear Layer Research Articles

Thicker Inner Nuclear Layer as a Predictor of Glaucoma Progression and the Impact of Intraocular Pressure Fluctuation.

Background: Thickening of the inner nuclear layer (INL) or microcystic macular changes has been reported to be implicated in glaucoma patients, but their potential impact on disease progression remains unclear. We investigated the relationship between baseline microcystic macular edema in the INL or INL thickness and subsequent visual field (VF) progression in glaucoma patients. Methods: This retrospective observational study included primary open-angle glaucoma with follow-up exceeding 3 years. We identified macular cystic changes through Spectralis optical coherence tomography and measured the INL thickness using automated segmentation. Glaucoma progression was determined using the Guided Progression Analysis program of the Humphrey filed analyzer, calculating the mean deviation (MD) changes (dB/year). Results: Microcystic macular changes were observed in 12 (7.5%) of 162 patients. Patients with microcystic macular change had thicker INL thickness than those without it (p = 0.010). Progressors had a higher probability of having microcystic macular changes and a thicker average INL thickness than nonprogressors (p = 0.003, p = 0.019). Thicker INL thickness was associated with faster VF progression based on MD slope (dB/year) in the multivariate regression analysis (p = 0.045). Additionally, greater intraocular pressure (IOP) fluctuation was found to be associated with both a thicker INL and the presence of microcystic changes in the multivariate regression analysis (p = 0.003, 0.028). Conclusions: Increased macular INL thickness indicative of INL changes was linked to subsequent VF progression in glaucoma patients. These findings suggest that retinal inner nuclear change could serve as an indicator of progressive glaucoma.

Inner nuclear layer and olfactory threshold are interlinked and reflect inflammatory activity in multiple sclerosis.

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

Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography.

PurposeProspective treatments for age-related macular degeneration and inherited retinal degenerations are commonly evaluated in the Royal College of Surgeons (RCS) rat before translation into clinical application. Historically, retinal thickness obtained through postmortem anatomic assessments has been a key outcome measure; however, utility of this measurement is limited because it precludes the ability to perform longitudinal studies. To overcome this limitation, the present study was designed to provide a baseline longitudinal quantification of retinal thickness in the RCS rat by using spectral-domain optical coherence tomography (SD-OCT).MethodsHorizontal and vertical linear SD-OCT scans centered on the optic nerve were captured from Long-Evans control rats at P30, P60, P90 and from RCS rats between P17 and P90. Total retina (TR), outer nuclear layer+ (ONL+), inner nuclear layer (INL), and retinal pigment epithelium (RPE) thicknesses were quantified. Histologic sections of RCS retina obtained from P21 to P60 were compared to SD-OCT images.ResultsIn RCS rats, TR and ONL+ thickness decreased significantly as compared to Long-Evans controls. Changes in INL and RPE thickness were not significantly different between control and RCS retinas. From P30 to P90 a subretinal hyperreflective layer (HRL) was observed and quantified in RCS rats. After correlation with histology, the HRL was identified as disorganized outer segments and the location of accumulated debris.ConclusionsRetinal layer thickness can be quantified longitudinally throughout the course of retinal degeneration in the RCS rat by using SD-OCT. Thickness measurements obtained with SD-OCT were consistent with previous anatomic thickness assessments. This study provides baseline data for future longitudinal assessment of therapeutic agents in the RCS rat.

Retinal glymphatic system: an explanation for transient retinal layer volume changes?

This scientific commentary refers to ‘Retinal inner nuclear layer volume reflects response to immunotherapy in multiple sclerosis’, by Knier et al. (doi:10.1093/brain/aww219) . A recent article in Brain by Gelfand et al. (2012) on the inner nuclear layer (INL) of the retina in multiple sclerosis triggered a lively exchange of Letters to the Editor. With the advent of optical coherence tomography (OCT), a forgotten autopsy observation was restored to the top of the research agenda in multiple sclerosis. Over 150 years ago, severe atrophy of the retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) was shown to be associated with only subtle changes in the INL whilst the outer retinal layers were completely preserved (Muller, 1857). Although Heinrich Muller was cautious in interpreting potential INL changes, he was more convinced about the existence of secondary (retrograde) axonal degeneration. ‘Die sogenannten Korner erschienen etwas kornig, doch war mir sehr zweifelhaft, ob dies als pathologische Veranderung anzusprechen sei, da man Aehnliches auch sonst zu Gesicht bekommt.’ This case was discussed on pages 92–98 and the citation taken from page 93 (Muller, 1857). For the contemporary translation it is important to refer back to the terminology of the time. There were three ‘Kornerschichten’ that correspond to the present day: ‘ganglion cell layer’, ‘inner nuclear layer’ and ‘outer nuclear layer’. Muller was not able to see the GCL and his comment is on the next nuclear layer, the INL: ‘The so called nuclei seemed more grainy, but I am rather doubtful if this should be interpreted as a (specific) pathological finding as one can see similar features in other situations’. Subsequent histological studies of the macaque monkey eye following experimental lesions to the afferent visual pathway provided evidence for retrograde trans-synaptic degeneration reaching the GCL with associated changes in the …

Microcystic Inner Nuclear Layer Changes and Retinal Nerve Fiber Layer Defects in Eyes with Glaucoma.

ObjectiveTo examine microcystic inner nuclear layer (INL) changes in glaucomatous eyes and to determine associated factors. DesignRetrospective, cross-sectional, observational study. MethodsTwo hundred seventeen eyes of 133 patients with primary open angle glaucoma (POAG), 41 eyes of 32 patients with preperimetric glaucoma and 181 normal eyes of 117 subjects were ultimately included. Microcystic INL lesions were examined with infrared fundus images and with 19 vertical spectral domain optical coherence tomography (SD-OCT) images in the macular area.ResultsMicrocystic INL changes were observed in 6.0% of eyes with POAG, but none of the normal eyes or eyes with preperimetric glaucoma showed microcystic INL changes. The proportion of eyes with advanced glaucoma was significantly larger (P = 0.013) in eyes with microcystic lesions than without. The visual field mean deviation (MD) slope was also significantly worse (P = 0.027) in eyes with microcystic lesions. No significant differences were observed in age, sex, refraction, axial length, intraocular pressure, or MD value between eyes with and without microcystic INL lesions. In several cases, microcystic INL lesions occurred along with glaucomatous visual field progression. The retinal nerve fiber layer (RNFL) thickness (P = 0.013) and ganglion cell layer (GCL) + inner plexiform layer thickness (P = 0.023) were significantly lower in areas with microcystic lesions than without. The INL was also significantly thicker (P = 0.002) in areas with microcystic lesions.ConclusionsMicrocystic INL lesions in glaucomatous eyes are closely associated with RNFL and GCL thinning and correlated with worse MD slope. These INL lesions may indicate focal and progressive damage in glaucoma.

Comparative study of the influence of silicone oil and heavy silicone on ultrastructure of rabbits' retina

Objective To investigate the medium and long-term influence of silicon oil versus heavy silicone oil on rabbit retinas. Methods 28 health standard rabbits were randomly divided into A, B and C groups, with 12, 12 and 4 rabbits respectively. All rabbits received routine vitrectomy and tamponade with silicone oil (group A), or heavy silicone oil (group B) or balanced salt solution (group C). After 4, 8, 12 and 24 weeks, the retinal b-wave amplitude was measured by ERG, posterior retinal thickness was measured by optical coherence tomography (OCT). Retinal ultrastructure and tissue morphology were observed by transmission electron microscopy and optical microscopy. Results Compare to group C, the b-wave amplitude decreased at 4 weeks after surgery, and decreased at 8 weeks after surgery for group B, and decreased at 8 weeks after surgery, and decreased at 24 weeks after surgery for group A. The decreases were greater in group B than group A at 8, 12, 24 weeks after surgery, the difference was statistically significant (P<0.05). The posterior retinal thickness of group A and B was thinner than group C at 24 weeks after surgery (P<0.05). The decreases were greater in group B than group A, the difference was statistically significant (P<0.05). Transmission electron microscopy and optical microscopy revealed severe pathological changes of retinal ultrastructure and morphology in group A and B rabbit eyes, at 12 weeks and 8 weeks after surgery respectively. The changes were more severe in group B and group A, including edema and necrosis in cone/rod cells, in disk membranes, mitochondria, cytoplasm, nucleus and other organelles. The morphological changes were also more severe in group B and group A, including degenerations of ganglion cell layer, inner nuclear layer changes. Those changes became more severe when the tamponade time extended. Conclusion The heavy silicone influence on visual function, ultrastructures, histomorphology of rabbit retinas is much worse than the silicon oil, and the effect is more significant with its time prolong. Key words: Silicone oils/adverse effects; Retina/ultrastructure; Retina/physiopathology; Animal experimentation

An autoradiographic analysis of postnatal cell proliferation in the normal and degenerative mouse retina.

AbstractLight microscopic autoradiography, following injection of tritiated thymidine, was used to study the postnatal development of cells in the inner nuclear layer (INL) of the normal and rd (C57BL/6J‐rd le) mouse retina. Specific attempts were made to determine whether some bipolar cell degeneration occurs in conjunction with previously noted photoreceptor cell degeneration in the retina of the mutant (rd) mouse. A differential count of cell types in the INL of both the central and peripheral retina indicates that the same ratio of bipolar cells to Müller cells (3:1) exists in the normal and the rd retina during postnatal development. The density of cells in the INL was similar in both groups during development and similar decreases in width of the INL occurred in the normal and rd mouse during maturation. In addition, autoradiographic analysis of the proliferation of postnatally forming bipolar cells suggested that the rd gene is not lethal to the bipolar cell population which forms after birth. The labeling index (percent labeled cells) in the INL, determined as a function of the date of 3H‐thymidine injection and assessed in the mature retina (day 41), was similar in both mice. Analysis of the number of silver grains/nucleus presented a more complete picture of how the progenitor pool of cells contributes to the cell types formed postnatally in the retinas of both mice.The conclusion that bipolar cell death does not occur to any significant degree in the retina of the rd also suggests that transneuronal degeneration does not occur in the retina of the mutant mouse during the period (up to day 41) when most of the photoreceptor cells die. The observation in both groups of mice that cell density remains constant between postnatal day 14 and day 41, while the width of the INL changes tremendously, suggests that there is a significant redistribution of cells during growth of the eyeball and/or cell death which occurs in all cell types found in the INL in both the normal and mutant mouse.