Foveal pit morphological changes in asymptomatic carriers of the G11778A mutation with Leber's hereditary optic neuropathy.

AIM: To investigate the foveal pit morphology changes in unaffected carriers and affected Leber's hereditary optic neuropathy (LHON) patients with the G11778A mutation from one family. METHODS: This study was a prospective cross-sectional study. Both eyes from 16 family members (age from 9 to 47y) with the G11778A mutation were analyzed and compared with 1 eye from 20 normal control subjects. Eleven family members with the G11778A mutation but without optic neuropathy were classified as unaffected carriers (n=22 eyes). Five family members (n=10 eyes) expressed the LHON phenotype and were classified as affected patients. Retinal images of all the subjects were taken by optical coherence tomography (OCT), and an automatic algorithm was used to segment the retina to eight layers. Horizontal and vertical OCT images centered on the fovea were used to measure intra-retinal layer thicknesses and foveal morphometry. RESULTS: Thicker foveal thickness, thinner foveal pit depth, and flatter foveal slopes were observed in unaffected carriers and affected LHON patients (all P<0.001). Further, the slopes of all four sectors in the LHON were flatter than those in the unaffected carriers (all P<0.001). Compared with the control group, affected LHON patients had a thinner retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer (GCL+IPL), and total retina (all P<0.01). The retinal nerve fiber layer (RNFL) of affected patients was 38.0% thinner than that of controls while the GCL+IPL was 40.1% thinner. CONCLUSION: The foveal pit morphology shows changes in both unaffected carriers and affects patients. RNFL and GCL+IPL are thinner in affected LHON patients but not in unaffected carriers.

Deep perifoveal vessel density as an indicator of capillary loss in high myopia.

OBJECTIVES: This study investigates the macular vasculature of both vascular layers in different degrees of myopia by optical coherence tomography angiography (OCTA). METHODS: One hundred and forty-five eyes of 145 healthy subjects with spherical equivalents (SE) ranging from +0.50 to -16.50 dioptres were divided into three groups. The foveal avascular zone (FAZ) area and vessel density (VD) of OCTA images were compared. RESULTS: Compared with other groups, high myopia had a larger FAZ and less perifoveal VD in both layers and less deep total VD. Compared with other myopia, high myopia had less total VD in the superficial layer and parafoveal VD in the deep layer. Between emmetropia and low myopia, there was a difference only in the deep parafoveal VD. Except for the parafoveal VD in both layers and the superficial total VD, there were significant correlations of the FAZ with axial length (AL) and SE as well as VD. The deep perifoveal VD was most associated with high myopia. CONCLUSIONS: An increased FAZ and decreased VD in both layers were correlated with AL elongation. The decreasing deep perifoveal VD was most associated with high myopia. OCTA may provide additional information regarding the progression of pathologies in high myopia.

Associated risk factors in the early stage of diabetic retinopathy.

BACKGROUND: To investigate the retinal capillary density (RCD) of the macula using optical coherence tomography angiography (OCT-A) in type 2 diabetic patients and to further determine the association with risk factors. METHODS: A total of 212 eyes from 212 subjects were recruited; subjects included diabetics with no retinopathy (NDR, n = 90 eyes), diabetics with mild retinopathy DR (MDR, n = 36 eyes), and healthy participants (Control, n = 86 eyes). All participants underwent OCT-A scanning. RCD was quantified by superficial and deep retinal capillary layers (SRCL and DRCL) from OCT-A images. RESULTS: RCD in SRCL and DRCL was lower in NDR (P < 0.001) as well as in MDR (P < 0.001) when compared with control eyes. Diabetic patients were subdivided according to individual risk factors, complications related to diabetes, and hyperglycemia. Diabetic patients showed lower RCD in both the SRCL and DRCL when compared with healthy controls. Diabetics with age > 55y, HbA1c > 7% had significantly reduced DRCL (P < 0.05) when compared with the other group of diabetics (age < 55y, HbA1c < 7%). Diabetics with a blood urea nitrogen (BUN) > 8.2 mmol/L had significantly reduced SRCL and DRCL when compared to the other group of diabetics. CONCLUSIONS: Risk factors including older age, higher level of HbA1c, LDL-C and BUN, were associated with lower RCDs found in type 2 diabetic patients with and without mild DR by OCT-A. The impairment of retinal capillary by OCT-A may play a key role in the early monitoring of management in diabetes.

Thickness changes in the corneal epithelium and Bowman's layer after overnight wear of silicone hydrogel contact lenses.

BACKGROUND: To investigate thickness changes in the corneal epithelium and Bowman's layer after overnight silicone hydrogel contact lens (CL) wear by using ultra-high resolution optical coherence tomography (UHROCT). METHODS: Eleven subjects without CL wearing history were recruited for this study. An UHROCT was used to measure the thickness of the epithelium (ET), Bowman's layer (BT), stroma (ST), and total cornea (CCT) at the center of both eyes. A silicone hydrogel CL was inserted in the right eye of each subject, and the fellow non-CL wearing left eye served as the control. The lens was inserted at 9:30 pm and removed at 8:00 am the next morning. The subjects were evaluated at 9:00 pm (baseline), 9:30 pm (lens insertion), 10:00 pm (before sleep), 7:00 am (waking), 7:30 am, and 8:00 am (lens removal). RESULTS: Compared to the lens insertion level, the ET of the lens-wearing eye increased by 5.73% at eye opening (P = 0.001). The ET of the non-CL wearing eye and the BT in both eyes did not change after overnight CL wear. Compared to baseline, the CCT of the lens-wearing eye increased by 2.87% upon waking (P = 0.003) and recovered 30 min later (P = 0.555). In contrast, compared to baseline, the CCT of the non-CL wearing eye did not increase upon waking (P = 0.105). CONCLUSIONS: By using UHROCT, we found that overnight CL wear induced different swelling responses in the various sublayers of the cornea. TRIAL REGISTRATION: Retrospectively registered. Registration number: ChiCTR1800015115 . Registered 07 March 2018.

Retinal Microvascular Impairment in the Early Stages of Parkinson's Disease.

Purpose: To detect the retinal microvascular impairment using optical coherence tomography angiography (OCT-A) in patients with Parkinson's disease (PD) and find a correlation between the microvascular impairment and the neuronal damage. Methods: This is a prospective, observational study including 49 eyes from 38 PD patients in their early stages and 34 eyes from 28 healthy controls with comparable age range. Macula microvasculature was evaluated with the spectral-domain optical coherence tomography (SD-OCT) angiography and intraretinal layer thickness evaluated with the SD-OCT. A custom algorithm was used for custom segmentation of retinal thickness and quantification of the superficial and deep microvascular density of the macula, respectively. Results: PD patients showed reduced microvascular density in most of the areas of the whole retina. In the superficial retinal capillary plexus, statistical difference (P < 0.01) was seen in the total annular zone (TAZ), superior, temporal, inferior, and nasal zones. In PD patients, there was a strong correlation between the average ganglion cell layer and inner plexiform (GCIP) thickness and the TAZ of the superficial microvascular density (r = 0.062, P = 0.032). Conclusion: We demonstrated that retinal microvascular density decreased in PD patients. The correlation between microvascular impairment in the superficial retinal capillary layer and GCIP thinning also revealed that the retinal microvascular abnormality may contribute to the neurodegeneration in PD patients. OCT-A with quantitative analysis offers a new path of study and will likely be useful in the future as an objective biomarker for detecting vessel impairment in early stages of PD.

Altered Macular Microvasculature in Neuromyelitis Optica Spectrum Disorders.

PURPOSE: To evaluate macular microvascular changes in neuromyelitis optica spectrum disorders (NMOSD) by using optical coherence tomography angiography (OCT-A) and investigate their correlations with neuroaxonal structural damage evaluated with spectral-domain OCT (SD-OCT). DESIGN: Cross-sectional study. METHODS: Twenty eyes of 20 patients with NMOSD and 21 eyes from 21 healthy controls were enrolled. OCT-A was used to obtain microvascular network images of the whole, superficial, and deep retinal capillary plexuses (WRCP, SRCP, and DRCP) in a 3-mm-diameter area around the macula. SD-OCT was used to obtain the intraretinal thickness. Custom automated algorithms quantified the thickness of the intraretinal layers as well as microvascular density of the retinal capillary layers. RESULTS: NMOSD patients showed significantly decreased microvascular density in both SRCP and DRCP (P < .05) compared to controls. The decreased microvascular density in SRCP and DRCP significantly correlated with the frequency of optic neuritis attack (P < .05). Both SRCP and DRCP microvascular density significantly correlated (P < .05) with retinal nerve fiber layer and ganglion cell layer with inner plexiform layer. SRCP microvascular density moderately correlated with visual acuity, while a stronger correlation was found between DRCP and visual acuity. CONCLUSIONS: Decreased microvascular density in NMOSD patients correlated with the worsening of their visual acuity. Correlation between microvascular impairment and neuroaxonal thinning revealed that retinal microvascular alteration may contribute to neuroaxonal loss in NMOSD patients. OCT-A with measurable analysis offers a new path of study and will likely be useful as an objective biomarker for detecting microvascular impairment in NMOSD.

Characteristics of Retinal Structural and Microvascular Alterations in Early Type 2 Diabetic Patients.

Purpose: To investigate early retinal structural and microvascular changes in patients with type 2 diabetes mellitus (DM) and to analyze relationships among the retinal structure, microvasculature, and choroid. Methods: Seventy-seven patients with type 2 DM (40 with no diabetic retinopathy [DR], 37 with nonproliferative diabetic retinopathy [NPDR]), and 34 control subjects were enrolled. Spectral-domain optical coherence tomography, operating in radial 18-line mode, obtained macular images of the eight intraretinal layers and the choroid. The same system was equipped with Angiovue to obtain angiography images of the whole, superficial, and deep retinal capillary layers (WRCL, SRCL, and DRCL) in a 3-mm-diameter area around the macula. Algorithms quantified the thicknesses of the intraretinal layers and choroid as well as fractal dimensions (Dbox values) of the retinal capillary layers. Pearson's correlation was used to analyze the relationships. Results: The choroidal thickness was significantly decreased in all the regions of the DM patients with no DR (P < 0.05). Compared to controls, the Dbox values of the SRCL and DRCL were significantly decreased in diabetic patients with no DR; however, only the nerve fiber layer in this group was slightly thinner than in the controls (P < 0.05). In the two diabetic groups, there was a weak correlation between the ganglion cell complex thickness and the SRCL (P < 0.05). Conclusions: In DM, changes of retinal microvasculature might occur earlier than changes in retinal structure. Thinning of the choroid may be the earliest sign in the diabetic patients with no clinical DR.

Inner Retinal Microvasculature Damage Correlates With Outer Retinal Disruption During Remission in Behçet's Posterior Uveitis by Optical Coherence Tomography Angiography.

Purpose: To quantify the inner retinal vascular changes that occur in the superficial and deep layers in patients with Behçet's disease (BD) in remission using optical coherence tomography angiography (OCTA) and to evaluate the associations with outer retinal structure. Methods: Nineteen eyes from 19 patients with BD in remission were enrolled, including 10 eyes with less than five ocular attacks (n < 5) and nine eyes with five or more attacks (n ≥ 5). The foveal avascular zone (FAZ) and global and regional vessel density (VD) in both layers were compared between BD eyes and normal eyes. Their outer retinal structure, including integrity of the ellipsoid zone (EZ), interdigitation zone (IZ), and outer retinal layer thickness were evaluated. Associations between the inner retinal vasculature and outer retinal disruption were sought. Results: Compared to normal eyes, except for the nasal region, all deep capillary VD values were lower in the BD groups, especially in the inferior region. In the superficial layer, the VD differences between groups were larger in capillaries than in small vessels. The FAZ in the n ≥ 5 group was larger than that in normal and the n < 5 groups in the deep layer. Greater disruption of EZ and IZ was correlated with decreasing global and regional deep capillary VD. Conclusions: BD Patients in remission had significant changes in the inner retinal vasculature that corresponded to the outer retinal disruption. Quantitative measurement by OCTA and algorithm might be useful for evaluation of the vasculature and pathologic changes in BD.

Characteristic of entire corneal topography and tomography for the detection of sub-clinical keratoconus with Zernike polynomials using Pentacam.

The study aimed to characterize the entire corneal topography and tomography for the detection of sub-clinical keratoconus (KC) with a Zernike application method. Normal subjects (n = 147; 147 eyes), sub-clinical KC patients (n = 77; 77 eyes), and KC patients (n = 139; 139 eyes) were imaged with the Pentacam HR system. The entire corneal data of pachymetry and elevation of both the anterior and posterior surfaces were exported from the Pentacam HR software. Zernike polynomials fitting was used to quantify the 3D distribution of the corneal thickness and surface elevation. The root mean square (RMS) values for each order and the total high-order irregularity were calculated. Multimeric discriminant functions combined with individual indices were built using linear step discriminant analysis. Receiver operating characteristic curves determined the diagnostic accuracy (area under the curve, AUC). The 3rd-order RMS of the posterior surface (AUC: 0.928) obtained the highest discriminating capability in sub-clinical KC eyes. The multimeric function, which consisted of the Zernike fitting indices of corneal posterior elevation, showed the highest discriminant ability (AUC: 0.951). Indices generated from the elevation of posterior surface and thickness measurements over the entire cornea using the Zernike method based on the Pentacam HR system were able to identify very early KC.

Macular Vascular Fractal Dimension in the Deep Capillary Layer as an Early Indicator of Microvascular Loss for Retinopathy in Type 2 Diabetic Patients.

Purpose: To determine the ability of fractal dimension to detect early changes in the retinal microvascular network imaged by optical coherence tomography angiography (OCT-A) in type 2 diabetic patients. Methods: Sixty-seven patients with type 2 diabetic mellitus (DM) (48 with no diabetic retinopathy [DR], 19 with minimal DR) and 40 control subjects. Macular OCT-A images of the superficial and deep retinal capillary layers in a 2.5-mm diameter concentric annular zone (excluding the foveal avascular zone) were subdivided into six annular rings and four quadrants. A custom automated algorithm was developed to quantify the complexity and density of the two retinal capillary layers by fractal analysis. Results: Compared to controls, the fractal dimensional parameter (Dbox) of the two retinal capillary layers in most regions was significantly lower in diabetic patients with minimal DR (P < 0.05). The Dbox of the diabetic patients with no DR was also decreased in most regions of the deep retinal capillary layer (P < 0.05), but not in the superficial retinal capillary layer (P > 0.05). Based on the receiver operating characteristic curve analysis, the Dbox values for the deep retinal capillary layer had the highest index to discriminate diabetic patients with and without minimal DR from controls. Conclusions: Fractal dimension based on OCT-A has the potential to quantitatively characterize retinal microvascular changes in the early stage of DM. Changes in the fractal dimension in the deep retinal capillary layer could be an early indicator of microvasculature changes associated with retinopathy in type 2 diabetic patients.

The Impact of Flap Creation Methods for Sub-Bowman's Keratomileusis (SBK) on the Central Thickness of Bowman's Layer.

PURPOSE: To determine the impact of flap creation methods for sub-Bowman's keratomileusis (SBK) on central Bowman's layer thickness. METHODS: SBK flaps were made by Moria microkeratome for 20 subjects and by femtosecond (FEMTO) laser for 21 subjects. Corneal sublayer thicknesses were measured by ultra-high resolution optical coherence tomography before SBK and at 1 day, 1 week, 2 weeks, and 1 month afterwards. Each subject was imaged twice on each visit. Thicknesses of central epithelium, Bowman's layer, flap, and total cornea were calculated using a custom-made automated image processing algorithm. The repeatability of sublayer thickness measurements was tested by the intraclass correlation coefficient (ICC) and by the coefficient of repeatability (CoR) at 1 week post-SBK. RESULTS: ICCs of the Moria and FEMTO groups were ≥ 0.959 and ≥ 0.961 respectively for all sublayer measurements. The segmentation CoRs were less than 6.78% and 5.63% respectively. For both groups, microdistortions were present in the epithelium and Bowman's layer after SKB. The flap thickness of the Moria group was 9.8 µm (95% confidence interval: 4.8 - 14.8 µm) thinner than the FEMTO group one day after SBK (independent samples t-test, P < 0.05). Bowman's layer became thicker by 1.6 ± 1.1 µm and 1.7 ± 1.6 µm one day post-SBK for the Moria and FEMTO groups (repeated ANOVA, P < 0.05) and then remained stable. Corneal and sublayer thickness were similar between the two groups. CONCLUSIONS: Central Bowman's layer thickness increased 1 day post-SBK. Flap creation by Moria microkeratome and femtosecond laser did not have significantly different impacts on Bowman's layer thickness following SBK. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) NO: ChiCTR-OCH-14004525.