Silent Information Regulator T1 in Aqueous Humor of Patients with Age-Related Macular Degeneration

Purpose: The purpose of this study is to compare the aqueous humor level of Silent Information Regulator T1 (SIRT1) between patients with Age-related Macular Degeneration (AMD) and cataract patients. Materials and Methods: Aqueous humor level of SIRT1 was measured by enzyme-linked immunosorbent assay in 13 patients with wet-type AMD (n=13, AMD group) and 13 patients with cataracts (cataract group). In addition, the thickness of each retinal layer was determined by optical coherence tomography. Results: The aqueous humor level of SIRT1 was significantly lower in the AMD group than in the cataract group (p=0.007). In the AMD group, the SIRT1 level was positively correlated with the thickness of the retinal ganglion cell layer (r=0.31) and the inner nuclear layer (r=0.76). Conclusion: The aqueous level of SIRT1 decreased as the ganglion cell layer and inner nuclear layer became thinner, suggesting that reduction of SIRT1 activity might be involved in the pathogenesis of this disease.

Smooth borders between inner nuclear layer and outer plexiform layer predict fewer macular edema recurrences in branch retinal vein occlusion

We hypothesized the smoothness of the border between the inner nuclear layer (INL) and outer plexiform layer (OPL) associates with the frequency of macular edema (ME) recurrences secondary to branch retinal vein occlusion (BRVO). Thirty-seven consecutive eyes with BRVO treated with anti-vascular endothelial growth factor (VEGF) injections at 1-year follow-up were included. We manually traced the border between the INL and OPL within the 1.5-mm vertical line from the fovea on optical coherence tomography (OCT) images at the initial visit. The jagged ratio (JR), the border length divided by the spline curve length, was calculated. We performed univariate and multivariate regression analyses, including JR, patient characteristics, number of cystoid spaces in the INL, INL area, and outer retina area. Multivariate regression analysis showed JR significantly correlates with the total number of anti-VEGF injections (P < 0.0001). Moreover, the mean JR was significantly lower in the nine eyes receiving two or fewer injections than in the 28 eyes receiving three or more injections (1.02 ± 0.01 vs. 1.13 ± 0.06, P < 0.0001). A smooth border between the INL and the OPL on OCT images at the initial visit may be a biomarker for fewer ME recurrences in eyes with BRVO.

Subclinical anterior optic pathway involvement in early multiple sclerosis and clinically isolated syndromes

Optical coherence tomography (OCT) is gaining increasing relevance in the assessment of patients with multiple sclerosis. Converging evidence point to the view that neuro-retinal changes, in eyes without acute optic neuritis, reflect inflammatory and neurodegenerative processes taking place throughout the CNS. The present study aims at exploring the usefulness of OCT as a marker of inflammation and disease burden in the earliest phases of the disease. Thus, a cohort of 150 consecutive patients underwent clinical, neurophysiological and brain MRI assessment as well as lumbar puncture as part of their diagnostic workup for a neurological episode suggestive of inflammatory CNS disorder; among those 32 patients had another previous misdiagnosed episode. For the present study, patients also received a visual pathway assessment (OCT, visual evoked potentials, visual acuity), measurement of CSF inflammatory markers (17 cytokines-chemokines, extracellular vesicles of myeloid origin), and dosage of plasma neurofilaments. Subclinical optic nerve involvement is frequently found in clinically isolated syndromes by visual evoked potentials (19.2%). OCT reveals ganglion cell layer asymmetries in 6.8% of patients; retinal fibre layer asymmetries, despite being more frequent (17.8%), display poor specificity. The presence of subclinical involvement is associated with a greater disease burden. Second, ganglion cell layer thinning reflects the severity of disease involvement even beyond the anterior optic pathway. In fact, the ganglion cell layer in eyes without evidence of subclinical optic involvement is correlated with Expanded Disability Status Scale, low contrast visual acuity, disease duration, brain lesion load, presence of gadolinium enhancing lesions, abnormalities along motor and somatosensory evoked potentials, and frequency of CSF-specific oligoclonal bands. Third, the inner nuclear layer thickens in a post-acute (1.1–3.7 months) phase after a relapse, and this phenomenon is counteracted by steroid treatment. Likewise, a longitudinal analysis on 65 patients shows that this swelling is transient and returns to normal values after 1 year follow-up. Notwithstanding, the clinical, MRI, serological and CSF markers of disease activity considered in the study are strictly associated with one another, but none of them are associated with the inner nuclear layer. Our findings challenge the current hypothesis that the inner nuclear layer is an acute phase marker of inflammatory activity. The present study suggests that instrumental evidence of subclinical optic nerve involvement is associated with a greater disease burden in clinically isolated syndrome. Neuro-retinal changes are present since the earliest phases of the disease and yield important information regarding the neurodegenerative and inflammatory processes occurring in the CNS.

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

Background Retinal inner nuclear layer (INL) and olfactory threshold (OT) are associated with inflammatory activity in multiple sclerosis (MS). Objective The 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. Methods We 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). Results Cross-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. Conclusions INL 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.

The formation of perifoveal cysts in idiopathic macular holes and their relationship with retinal blood flow

Background : To study the formation and distribution of perifoveal cysts in an idiopathic macular hole and their correlation with retinal blood flow. Method: There were 16 patients in the small hole group, and 23 patients in the large hole group. In the preoperative procedure, we measured the number, the total area and the average size of the cysts in the inner nuclear layer, outer plexiform and Henle fiber layer complex around the hole; and the vascular density of the retinal capillary plexuses of all cases. Postoperatively, we measured the retinal capillary plexuses vascular density in 17 eyes. Results: The number and the total area of the cysts in the inner nuclear layer of the large hole group were greater than those of the small hole group (t=-2.882, P =0.007, t= -3.412 P =0.002). And we came to the same conclusion in the outer plexiform and Henle fiber layer complex (t=-3.935 P =0.000, t=-4.335 P =0.000). The average cystic area of the inner nuclear layer and outer plexiform and Henle fiber layer complex had no significant difference between the two groups (t=0.178 P =0.860, t=-1.767 P =0.085). There was a significant correlation among the idiopathic macular hole diameter, the number and the total area of cysts in the outer plexiform and Henle fiber layer complex, the vascular density of the retinal superficial capillary plexuses and deep capillary plexuses; the respective coefficients were -0.725, -0.474, -0.314, -0.768, and +0.624. Conclusions: 1. The diameter of the idiopathic macular hole was related to the formation of cysts around the hole. 2. Multiple mechanisms are involved in the interaction between the cystic space around the idiopathic macular hole and the retinal capillary plexuses.