Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children

PurposeAssociation of SIX1-SIX6 variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications.Methods2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression.ResultsSNPs rs33912345 (p=7.7×10−4) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8–9 year-old group for rs33912345 (p=5.2×10−4) and rs10483727 (p=3.3×10−4). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (β=1.66; p=0.0059), but not rs33912345-C (β=1.31; p=0.052) or rs10483727-T (β=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL.ConclusionsBoth rs33912345 and rs10483727 at SIX1-SIX6 were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6 in RNFL variation during neural retina development in childhood.

Association of progressive optic disc tilt with development of retinal nerve fibre layer defect in children with large cup-to-disc ratio

Background/aimsWhereas myopic optic disc deformation has been posited as a risk factor for glaucomatous damage, longitudinal studies evaluating their association have been sparse. We investigated whether the optic nerve head (ONH)’s morphological alteration during myopia progression play any role in development of retinal nerve fibre layer defect (RNFLD) in children with a large vertical cup-to-disc ratio (vCDR).MethodsSixty-five normotensive eyes of 65 children aged under 8 years with (1) vCDR ≥0.5 but no additional signs of glaucoma and (2) who could be tracked at young adulthood (18–28 years) were included. Children’s spherical equivalent (SE), intraocular pressure, vCDR and optic disc tilt ratio were recorded. Rare events logistic regression analysis was employed to identify factors associated with RNFLD-development risk.ResultsThe study group’s mean age was 5.4±1.3 years, its average vCDR was 0.62±0.07, and the average SE was −0.3±1.4 dioptres ((D), range −3.15 to 2.75D) at the baseline. After an average follow-up of 16.1±3.0 years, the mean vCDR was 0.64±0.09, and the mean SE, −3.2±2.2D (range −7.25 to 0.00 D). Among the 65 eyes, 12 (18.5%) developed RNFLD. A greater SE change (OR=1.737, p=0.016) and a greater increase in tilt ratio (OR=2.364, p=0.002) were both significantly associated with higher RNFLD-development risk.ConclusionIn this cohort of Korean children with large vCDR, progressive optic disc tilt in the course of myopia progression was associated with higher RNFLD-development risk. This finding suggests that morphological alterations in the ONH during axial elongation might represent an underlying susceptibility to glaucomatous damage in large-vCDR children.

Factors Associated with Changes in Peripapillary Retinal Nerve Fibre Layer Thickness in Healthy Myopic Eyes

Myopic people face an elevated risk of primary open angle glaucoma. Changes in the fundus in people with high myopia often lead to misdiagnosis of glaucoma, as this condition has many clinical signs in common with myopia, making the diagnosis of glaucoma more challenging. Compared to reduction of the visual field, a decrease in retinal nerve fibre layer (RNFL) thickness occurs earlier in glaucoma, which is widely considered useful for distinguishing between these conditions. With the development of optical coherence tomography (OCT), RNFL thickness can be measured with good reproducibility. According to previous studies, this variable is not only affected by axial length but also related to the patient’s age, gender, ethnicity, optic disc area, and retinal blood flow in myopia. Herein, we intend to summarize the factors relevant to the RNFL in myopia to reduce the false-positive rate of glaucoma diagnosis and facilitate early prevention of myopia.

Evaluation of retinal nerve fibre layer thickness as a possible measure of diabetic retinal neurodegeneration in the EPIC-Norfolk Eye Study

Background/aimsMarkers to clinically evaluate structural changes from diabetic retinal neurodegeneration (DRN) have not yet been established. To study the potential role of peripapillary retinal nerve fibre layer (pRNFL) thickness as a marker for DRN, we evaluated the relationship between diabetes, as well as glycaemic control irrespective of diabetes status and pRNFL thickness.MethodsLeveraging data from a population-based cohort, we used general linear mixed models (GLMMs) with a random intercept for patient and eye to assess the association between pRNFL thickness (measured using GDx) and demographic, systemic and ocular parameters after adjusting for typical scan score. GLMMs were also used to determine: (1) the relationship between: (A) glycated haemoglobin (HbA1c) irrespective of diabetes diagnosis and pRNFL thickness, (B) diabetes and pRNFL thickness and (2) which quadrants of pRNFL may be affected in participants with diabetes and in relation to HbA1c.Results7076 participants were included. After controlling for covariates, inferior pRNFL thickness was 0.94 µm lower (95% CI −1.28 µm to −0.60 µm), superior pRNFL thickness was 0.83 µm lower (95% CI −1.17 µm to −0.49 µm) and temporal pRNFL thickness was 1.33 µm higher (95% CI 0.99 µm to 1.67 µm) per unit increase in HbA1c. Nasal pRNFL thickness was not significantly associated with HbA1c (p=0.23). Similar trends were noted when diabetes was used as the predictor.ConclusionSuperior and inferior pRNFL was significantly thinner among those with higher HbA1c levels and/or diabetes, representing areas of the pRNFL that may be most affected by diabetes.

Retinal Nerve Fibre Layer Thickness Change Following Femtosecond Laser-Assisted in situ Keratomileusis

Purpose: To evaluate the effect of femtosecond laser-assisted in situ keratomileusis (FS-LASIK) on retinal fovea thickness, volume, and retinal nerve fibre layer (RNFL) thickness.Methods: Thirty-seven eyes (37 patients) undergoing FS-LASIK were included in this prospective study. Optical coherence tomography (OCT) was performed 1 day before, 1 h and 1 day after FS-LASIK surgery.Result: Eighteen male and nineteen females were enrolled. Mean patient age was 22.94 ± 4.22 years. One hour postoperatively, macula fovea thicknesses, macula fovea volume, macula parafovea thickness, macula parafovea volume, macula perifovea thickness, macula perifove volume, temporal RNFL thickness, and superior RNFL thickness measures showed significant decrease (t = 6.171, 6.032, and 9.837, 9.700, 2.532, 4.393, 4.926, 2.265; p = 0.000, 0.000, 0.000, 0.000, 0.016, 0.000, 0.000, and 0.011). Day 1 post-operation, macula fovea thicknesses, macula fovea volume, macula parafovea thickness, macula parafovea volume, and inferior RNFL thickness measures showed significant change compared to preoperative measures (t = 3.620, 3.220, 2.901, 2.910, 3.632; p = 0.001, 0.003, 0.006, 0.006, and 0.001).Conclusion: Our data suggest there are alterations in retinal foveal and RNFL measurements by OCT 1 h and 1 day after FS-LASIK surgery.

A rare case of bilateral ocular manifestations of Sturge-Weber syndrome

Sturge–Weber syndrome (SWS) is a group of phakomatoses characterized by hamartomas involving brain, skin and eyes. A 36 years old female presented with pain and diminution of vision in both eyes since last 1 year. On examination she has bluish sclera in B/L eyes with characteristic facial port-wine stain. Best corrected visual acuity (BCVA) in R/E- 6/18, N6 and in L/E- 6/6, N6. Intra-occular pressure (IOP) in R/E – 27 mm Hg and in L/E –18 mmHg. On gonioscopy – open angle B/E. On direct ophthalmoscopy and slit-lamp examination with 90 D lens, cup-disc ratio in R/E – 0.9 and in L/E – 0.7 with thinning of neuro-retinal rim in B/E. In optical coherence tomography (OCT), retinal nerve fibre layer (RNFL) and optic nerve head (ONH) it was confirmed. Other systemic examination – within normal limit. Initially, she had been on conservative treatment. As intraocular pressure remained high after several weeks of treatment, trabeculectomy in R/E done under local anaesthesia. No post-operative complications were seen. After 7 days of follow-up IOP – within normal limit, vision in R/E unchanged and had been frequently followed-up.

A review of ocular perfusion pressure and retinal thickness: A case for the role of systemic hypotension in glaucoma

Background: Ocular perfusion pressure (OPP) is defined as blood pressure (BP) minus intraocular pressure (IOP). Low OPP may result in decreased ocular blood flow (OBF) and oxygen to the optic nerve head (ONH) and retina.Aim: To review the role of systemic hypotension and similar conditions in OPP and its influence on retinal nerve fibre layer (RNFL) thickness and the ganglion cell complex (GCC).Method: A literature search was conducted using the following search terms: ‘systemic hypotension’; ‘glaucoma’; ‘retinal nerve fibre layer’; ‘optic nerve’; ‘ocular blood flow’ and ‘ocular perfusion pressure’.Results: The Los Angeles Eye Study and Barbados Eye Study found that decreased OPP and BP increased the risk of glaucoma development by up to six times. Reduced retinal perfusion with resultant thinning of the RNFL in conditions with a similar mechanism, such as obstructive sleep apnoea syndrome, has indicated the importance of reduced OPP in retinal thickness. In the absence of any study directly showing the effect of systemic hypotension on OPP and retinal thickness, a working hypothesis proposes that reduced BP with or without normal-to-raised IOP will reduce OPP. The reduced OPP and OBF in those with systemic hypotension may result in oxidative stress and hypoxia which may then cause retinal ganglion cell death and the resultant retinal thinning.Conclusion: The increased risk of glaucoma development and progression relating to decreased BP and OPP has been proven to be of importance. Monitoring patients with systemic hypotension and evaluating the macula, ONH RNFL and GCC thickness may alert clinicians to possible glaucomatous changes.

The Retina in Patients With Triple A Syndrome: A Window Into Neurodegeneration?

ObjectiveExperimental evidence suggests that the clinical manifestations of Triple A syndrome result from oxidative stress. Several conditions caused by oxidative stress display retinal involvement. Our objective was to assess the retina and optic nerve involvement in children with Triple A syndrome.MethodsEleven patients with genetically proven Triple A syndrome followed-up in our centre were approached for study participation. The main outcome was the measurement of the thicknesses of the different retinal layers by Optical Coherence Tomography (OCT).Results9 patients with triple A syndrome had OCT measurements. 7 patients were children and 2 were adults; 4 were females and 5 were males. The 7 paediatric patients had at least two OCT measured at a mean interval of 7.9 months after the first one. The average Retinal Nerve Fibre Layer thickness was 74 ± 10 µm in patients compared to the paediatric reference range of 100 ± 2 µm (p&lt;0.05).Conclusions and RelevanceThis is the first study to document retinal layer thicknesses in a series of patients with Triple A syndrome. Nearly all retinal thickness and peripapillary RNFL measurements were very significantly inferior to the reference range in Triple A patients, whatever their age. RNFL thinning was more marked at the temporal part of the optic nerve. OCT being non-invasive, it represents a promising tool to assess the severity of neurodegeneration in patients with Triple A syndrome.