In Vivo Confocal Microscopy Evaluation in Patients with Keratoconus

Keratoconus is the most common primary corneal ectasia characterized by progressive focal thinning. Patients experience increased irregular astigmatism, decreased visual acuity and corneal sensitivity. Corneal collagen crosslinking (CXL), a minimally invasive procedure, is effective in halting disease progression. Historically, keratoconus research was confined to ex vivo settings. In vivo confocal microscopy (IVCM) has been used to examine the corneal microstructure clinically. In this review, we discuss keratoconus cellular changes evaluated by IVCM before and after CXL. Cellular changes before CXL include decreased keratocyte and nerve densities, disorganized subbasal nerves with thickening, increased nerve tortuosity and shortened nerve fibre length. Repopulation of keratocytes occurs up to 1 year post procedure. IVCM also correlates corneal nerve status to functional corneal sensitivity. Immediately after CXL, there is reduced nerve density and keratocyte absence due to mechanical removal of the epithelium and CXL effect. Nerve regeneration begins after 1 month, with nerve fibre densities recovering to pre-operative levels between 6 months to 1 year and remains stable up to 5 years. Nerves remain tortuous and nerve densities are reduced. Corneal sensitivity is reduced immediately postoperatively but recovers with nerve regeneration. Our article provides comprehensive review on the use of IVCM imaging in keratoconus patients.

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.

The Influence of Smoking on Choroidal, Macular and Retinal Nerve Fiber Layer Thickness

Background: Smoking is one of the most serious health hazards because it affects every organ in our bodies. Cigarette smoking increases the chance of developing systemic and ocular vascular diseases significantly. Although the exact mechanism behind the association between ocular vascular disorders and smoking are unknown, the peripheral vasoconstriction action of nicotine is believed to lead to an increase in peripheral blood flow resistance. This study was designed to examine the impact of smoking with Spectral Domain Optical Coherence Tomography (SD-OCT) on the peripapillary retinal nerve fibre (RNFL), macular, and choroidal thickness. Methods: This prospective study was done on 50. It included 25 healthy cigarette smokers with no systemic or ocular illness and another 25 age- and gender-matched healthy non-smokers. Results: The smoking group had a substantial reduction in central macular and choroidal thickness as compared to the nonsmoker group. The RNFL peripapillary thickness across groups was not significantly altered, with the exception of the temporal (T) quadrant which was significantly thinner in the smoking group. This study discovered a substantial negative correlation between peripapillary RNFL, central macular thickness, and smoking exposure. Conclusions: Smoking reduces the mean thickness of the peripapillary retinal nerve fibre layer (particularly in the temporal quadrant), the choroidal layer, and the central macular layer statistically significantly.

Corneal nerve loss as a surrogate marker for poor pial collaterals in patients with acute ischemic stroke

In patients with acute ischemic stroke, pial collaterals play a key role in limiting neurological disability by maintaining blood flow to ischemic penumbra. We hypothesized that patient with poor pial collaterals will have greater corneal nerve and endothelial cell abnormalities. In a cross-sectional study, 35 patients with acute ischemic stroke secondary to middle cerebral artery (MCA) occlusion with poor (n = 12) and moderate-good (n = 23) pial collaterals and 35 healthy controls underwent corneal confocal microscopy and quantification of corneal nerve and endothelial cell morphology. In patients with MCA stroke, corneal nerve fibre length (CNFL) (P < 0.001), corneal nerve fibre density (CNFD) (P = 0.025) and corneal nerve branch density (CNBD) (P = 0.002) were lower compared to controls. Age, BMI, cholesterol, triglycerides, HDL, LDL, systolic blood pressure, NIHSS and endothelial cell parameters did not differ but mRS was higher (p = 0.023) and CNFL (p = 0.026) and CNBD (p = 0.044) were lower in patients with poor compared to moderate-good collaterals. CNFL and CNBD distinguished subjects with poor from moderate-good pial collaterals with an AUC of 72% (95% CI 53–92%) and 71% (95% CI 53–90%), respectively. Corneal nerve loss is greater in patients with poor compared to moderate-good pial collaterals and may act as a surrogate marker for pial collateral status in patients with ischemic stroke.