Repeatability and agreement of AOCT-1000 M, RTVue XR and IOL master 500 in measuring corneal thickness mapping and axial length applying principle of optical coherence tomography.

PURPOSE: To evaluate the repeatability and agreement of Fourier-domain optical coherence tomography (AOCT-1000 M and RTVue XR) and partial coherence interferometry biometer (IOL Master 500) in measuring corneal thickness mapping and axial length respectively. METHODS: Corneal thickness was measured by AOCT-1000 M and RTVue XR. Axial lengths were measured by AOCT-1000 M and IOL Master 500. The repeatability and agreement of corneal thickness and axial length were calculated in two groups of devices. The intraclass correlation coefficient (ICC) was used to verify the repeatability of the device. The 95% confidence interval of the difference compared to the set cut-off value was used to verify the agreement between the two devices. RESULTS: A total of 60 subjects with 58 eyes were included. The central corneal thickness measured by AOCT-1000 M and RTVue XR were 504.46 ± 42.53 µm and 504.43 ± 42.89 µm respectively. The average difference between groups was 0.03 ± 4.58 µm, and the 95% confidence interval was (-1.17, 1.24), which was far less than the set threshold value of 15 µm (P < 0.001). Both RTVue XR and AOCT-1000 M had very good ICC values of central corneal thickness (0.998 and 0.994, respectively). The average axial lengths measured by AOCT-1000 M and IOL Master 500 were 24.28 ± 1.25 mm and 24.29 ± 1.26 mm respectively and the 95% confidence interval was (-0.02, 0.01), which was less than the set threshold value of 0.15 mm (P < 0.001). The ICC for both devices were 1.000. CONCLUSION: Good repeatability and agreement were seen in measurements of central corneal thickness and axial length by AOCT-1000 M.

Best-corrected visual acuity results facilitate molecular diagnosis of infantile nystagmus patients harboring FRMD7 mutations.

The visual function of patients with infantile nystagmus (IN) can be significantly decreased owing to constant eye movement. While, reaching a definitive diagnosis becomes a challenge due to genetic heterozygous of this disease. To address it, we investigated whether best-corrected visual acuity (BCVA) results can facilitate the molecular diagnosis of IN patients harboring FRMD7 mutations. 200 patients with IN from 55 families and 133 sporadic cases were enrolled. Mutations were comprehensively screened by direct sequencing using gene-specific primers for FRMD7. We also retrieved related literature to verify the results based on our data. We found that the BCVA of patients with IN harboring FRMD7 mutations was between 0.5 and 0.7, which was confirmed by data retrieved from the literature. Our results showed that BCVA results facilitate the molecular diagnosis of patients with IN harboring FRMD7 mutations. In addition, we identified 31 FRMD7 mutations from the patients, including six novel mutations, namely, frameshift mutation c.1492_1493insT (p.Y498LfsTer14), splice-site mutation c.353C > G, three missense mutations [c.208C > G (p.P70A), c.234G > A (p.M78I), and c.1109G > A (p.H370R)], and nonsense mutation c.1195G > T (p.E399Ter). This study demonstrates that BCVA results may facilitate the molecular diagnosis of IN patients harboring FRMD7 mutations.

Performance of the AIDRScreening system in detecting diabetic retinopathy in the fundus photographs of Chinese patients: a prospective, multicenter, clinical study.

Background: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population worldwide, and there is a large unmet need for DR screening in China. This observational, prospective, multicenter, gold standard-controlled study sought to evaluate the effectiveness and safety of the AIDRScreening system (v. 1.0), which is an artificial intelligence (AI)-enabled system that detects DR in the Chinese population based on fundus photographs. Methods: Participants with diabetes mellitus (DM) were recruited. Fundus photographs (field 1 and field 2) of 1 eye in each participant were graded by the AIDRScreening system (v. 1.0) to detect referable DR (RDR). The results were compared to those of the masked manual grading (gold standard) system by the Zhongshan Image Reading Center. The primary outcomes were the sensitivity and specificity of the AIDRScreening system in detecting RDR. The other outcomes evaluated included the system's diagnostic accuracy, positive predictive value, negative predictive value, diagnostic accuracy gain rate, and average diagnostic time gain rate. Results: Among the 1,001 enrolled participants with DM, 962 (96.1%) were included in the final analyses. The participants had a median age of 60.61 years (range: 20.18-85.78 years), and 48.2% were men. The manual grading system detected RDR in 399 (41.48%) participants. The AIDRScreening system had a sensitivity of 86.72% (95% CI: 83.39-90.05%) and a specificity of 96.09% (95% CI: 94.14-97.54%) in the detection of RDR, and a false-positive rate of 3.91%. The diagnostic accuracy gain rate of the AIDRScreening system was 16.57% higher than that of the investigator, while the average diagnostic time gain rate was -37.32% lower. Conclusions: The automated AIDRScreening system can detect RDR with high accuracy, but cannot detect maculopathy. The implementation of the AIDRScreening system may increase the efficiency of DR screening.

Relationship Between Cone Loss and Microvasculature Change in Retinitis Pigmentosa.

Purpose: To objectively quantify cone density (CD) and microvascular density (MVD) in normal subjects and patients with moderate or severe retinitis pigmentosa (RP) by adaptive optics (AO) and optical coherence tomography angiography (OCTA) and to evaluate the changes in the parafoveal regions. Method: Thirty-seven eyes from 20 RP patients and 54 eyes from 29 age-matched healthy participants underwent AO fundus and OCTA imaging. AO images covering a 3-mm-diameter area centered on the fovea were subdivided into 5 equidistant concentric rings (C1-C5). An automated algorithm was used to quantify the mean cone density (mCD; cells/mm2). Macular MVDs (%) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were assessed by OCTA. Results: In the moderate RP group, CDs in C2 and C3 were each significantly lower than in the normal group (both P < 0.05). In the severe RP group, CDs were significantly lower than in normal eyes in each concentric ring (all P < 0.001; C1-C5). In both RP groups, MVDs were significantly lower than in normal eyes for both the SCP and DCP (both P < 0.05). The mean CD was significantly correlated with the MVD in the DCP (r = 0.43; P = 0.028) but not in the SCP (r = -0.19, P = 0.323). Conclusions: Decreased CD was present in the moderate and severe RP groups. This was accompanied by a decreased MVD in the DCP. Direct assessment of photoreceptors in RP patients by high-resolution imaging technologies is crucial for the future development of RP therapeutics.

Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus.

OBJECTIVES: Infantile nystagmus (IN) is a genetically heterogeneous condition characterised by involuntary rhythmic oscillations of the eyes accompanied by different degrees of vision impairment. Two genes have been identified as mainly causing IN: FRMD7 and GPR143. The aim of our study was to identify the genetic basis of both sporadic IN and X-linked IN. DESIGN: Prospective analysis. PATIENTS: Twenty Chinese patients, including 15 sporadic IN cases and 5 from X-linked IN families, were recruited and underwent molecular genetic analysis. We first performed PCR-based DNA sequencing of the entire coding region and the splice junctions of the FRMD7 and GPR143 genes in participants. Mutational analysis and co-segregation confirmation were then performed. SETTING: All clinical examinations and genetic experiments were performed in the Eye Hospital of Wenzhou Medical University. RESULTS: Two mutations in the FRMD7 gene, including one novel nonsense mutation (c.1090C>T, p.Q364X) and one reported missense mutation (c.781C>G, p.R261G), were identified in two of the five (40%) X-linked IN families. However, none of putative mutations were identified in FRMD7 or GPR143 in any of the sporadic cases. CONCLUSIONS: The results suggest that mutations in FRMD7 appeared to be the major genetic cause of X-linked IN, but not of sporadic IN. Our findings provide further insights into FRMD7 mutations, which could be helpful for future genetic diagnosis and genetic counselling of Chinese patients with nystagmus.

The impact of eyelid and eye contour factors on a toric soft contact lens fitting in Chinese subjects.

PURPOSE: To evaluate eyelid and eye contour factors that can influence the fitting of toric soft contact lenses (TSCLs). METHODS: Thirty-two subjects (64 eyes) were enrolled and fitted with Lo-Torque design TSCLs. One eye of each subject was randomly selected. High-resolution digital images were acquired after the subjects had worn the lens for 20 minutes, and the images were then processed with Adobe Photoshop. The palpebral aperture (PA), various angles of the eyelid, horizontal visible iris diameter (HVID), and lens parameters were obtained. Finally, lens fitting was evaluated. RESULTS: During the assessment of the correlations between the eyelid and eye contour factors and the lens fitting, there were four pairs of significant correlations: (1) the PA and rotational direction of the lens: larger eye PA was associated with a greater possibility of nasal rotation of the corresponding lens (P=0.03); (2) the angle of the central lower lid (θ3) and the rotational stability of the lens: the larger the angle was, the worse the rotational stability was (P=0.02); (3) the lower lid angle of the medial canthus (θ5) and temporal rotational recovery: the smaller the angle was, the more quickly the lens recovered (P=0.05); and (4) HVID and routine fitting assessments: the larger the HVID was, the looser the lens fitting (P=0.00). Finally, when assessing correlations between some lens parameters and the orientation of the lens, we found that lower sphere values were associated with quicker lens recovery (P=0.04). CONCLUSION: Several eye factors, as well as lens characteristics, had impacts on the TSCLs fitting, including the PA, the angle of the central lower lid (θ3), the lower lid angle of the medial canthus (θ5), and the sphere of the lens. These factors should receive particular attention when fitting TSCLs.

Clinical significance of tear menisci in dry eye.

PURPOSE: To determine the relationships among tear menisci variables and clinical tests used in the diagnosis of dry eye patients. METHODS: Dry eye patients (n=50; age, 35.2 years) and healthy subjects (n=48; age, 33.3 years) were recruited. Upper and lower tear menisci were imaged noninvasively by optical coherence tomography (OCT) immediately after normal and delayed blinking in both eyes. Tear meniscus heights, areas, and radius of curvatures were obtained by custom software. Tear film break-up time was measured by fluorescein (fluorescein film tear break-up time, FTBUT) and tearscope (noninvasive tear film break-up time), ocular surface vital staining was evaluated with fluorescein (FS), and secretion was measured by Schirmer I test without and with anesthesia. RESULTS: In dry eye patients, all lower tear meniscus variables during normal blinking were correlated with all clinical tests except Schirmer I test without anesthesia. Upper tear meniscus variables were correlated with FTBUT and Schirmer I test with anesthesia. During delayed blinking, upper and lower tear menisci variables were correlated with Schirmer I test without anesthesia and FS; however, there were no correlations between menisci variables and FTBUT or Schirmer I test with anesthesia. In healthy subjects, only lower meniscus variables were correlated with Schirmer I test with anesthesia during normal blinking. During delayed blinking, the lower meniscus variables were correlated with only the Schirmer I test without anesthesia. CONCLUSIONS: Lower tear menisci were correlated more strongly with the clinical tests than were upper menisci. The tear menisci were associated with the basic tear secretion during normal blinking. Delayed blinking may affect reflex tearing levels.

Tear menisci after overnight contact lens wear.

PURPOSE: To determine the effect of overnight wear of contact lenses (CL) on tear meniscus, tear film stability, and subjective comfort. METHODS: Sixty asymptomatic subjects were divided into three groups. The control group was composed of 20 non-CL wearers. Twenty inexperienced and 20 experienced CL wearers were enrolled as group 1 and group 2. For each subject in groups 1 and 2, a hydrogel and a silicone hydrogel CL were randomly assigned to each eye. Optical coherence tomography was used to determine volumes of the upper and lower tear menisci. Tear film stability was determined by non-invasive tear break-up time (NITBUT) measured by tearscope. A previously used questionnaire assessed dry eye symptoms. Subjects were evaluated during an 11-h period, including immediately before and after sleeping. RESULTS: Compared with the presleep levels, tear meniscus volume in the control group increased immediately after awakening and recovered by 1 hour later (p < 0.05). In contrast, tear meniscus volume in lens wearers increased on eye opening and recovered by 10 min later (p < 0.05). Tear meniscus volumes in CL wearers were less than those in controls at eye opening. NITBUT and comfort scores decreased immediately after CL insertion (p = 0.00). After eye opening, NITBUT was larger than the presleep levels until 10 min later. The comfort score was lower than the presleep values until 5 min later. CONCLUSIONS: Dynamic changes in the tear menisci, NITBUT, and comfort level were evident in both inexperienced and experienced CL wearers during and after overnight wear. Decreased tear meniscus volumes and tear film stability may contribute to lower eye comfort for extended CL wearers. The tearing on eye opening may facilitate improvement of ocular comfort and tear refreshment for a reconditioning of the tear system and the CL.

Corneal biomechanical properties and intraocular pressure in high myopic anisometropia.

OBJECTIVES: To investigate corneal biomechanical properties and intraocular pressure (IOP) in patients with high myopic anisometropia. METHODS: Patients with high myopic anisometropia (n = 23) and emmetropic subjects (n = 55) were enrolled. Corneal hysteresis (CH), Goldmann-correlated intraocular pressure (IOPg), corneal resistance factor, and corneal-compensated IOP (IOPcc) were measured with Ocular Response Analyzer. Central corneal thickness was measured by optical coherence tomography. Zeiss IOL-Master determined the values of corneal refractive power and ocular axial length. RESULTS: Significant differences were presented in CH, IOPg, and IOPcc among the high myopic, contralateral, and normal eyes (analysis of variance, P<0.05). CH in high myopic eye was lower than that in the other two groups (post hoc, P<0.05), whereas IOPg and IOPcc in both eyes of anisometropic myopia were higher compared with the normal subjects (post hoc, P<0.01). CH was associated with central corneal thickness and axial length in high myopic eyes. All measured biometric parameters showed significant correlations between two eyes in high myopic anisometropia. CONCLUSIONS: High myopic eyes showed decreased CH, but not corneal resistance factor, which indicates that some aspects of corneal biomechanical properties may be altered in high myopic eye of anisometropia. It is also suggested that anisometropic eyes with different refractive errors do not share the same biomechanical properties, which may impact IOP measurement.

Upper punctal occlusion versus lower punctal occlusion in dry eye.

PURPOSE: To compare the effectiveness of upper punctal occlusion versus that of lower punctal occlusion in dry eye patients. METHODS: One eye's upper punctum and the contralateral eye's lower punctum were occluded with collagen plugs in 20 dry eye patients. The same procedure was performed in 20 normal subjects. The upper and lower tear menisci were imaged simultaneously by real-time OCT before punctal occlusion and repeated on days 1, 4, 7, and 10 afterward. The subjective symptom score, corneal fluorescein staining intensity, Schirmer I test result, and tear breakup time (TBUT) were also determined. RESULTS: In dry eye patients, occlusion of either punctum improved symptom scores, fluorescein staining scores, TBUT, and lower tear meniscus height (LTMH, P < 0.05); however, Schirmer test scores and upper tear meniscus height (UTMH) did not change after occlusion (P > 0.05). There was no significant difference for any of these variables between upper punctum- and lower punctum-occluded eyes, before or after occlusion (P > 0.05). In normal subjects, Schirmer test scores, TBUT, UTMH, and LTMH did not change over time (P > 0.05). CONCLUSIONS: Punctal occlusion with collagen plugs in dry eye patients leads to the relief of subjective symptoms and the improvement of objective signs. The effectiveness of occluding the upper or lower punctum is similar. The LTMH is a valid indicator of the success of punctal occlusion.

Diurnal variation of ocular hysteresis, corneal thickness, and intraocular pressure.

PURPOSE: To investigate, in healthy Asian subjects, the diurnal changes of the corneal biomechanical properties of corneal hysteresis (CH) and its relation to fluctuations of intraocular pressure (IOP) and central corneal thickness (CCT) after sleeping. METHODS: Forty eyes of 20 healthy Asian volunteers (4 males and 16 females) with a mean age of 19.7 +/- 1.1 years were measured with a modified retinal optical coherence tomography and an ocular response analyzer (ORA). CH, CCT, Goldmann-equivalent intraocular pressure (IOPg), corneal resistance factor (CRF), and corneal compensated intraocular pressure (IOPcc) were obtained. Repeated measurements were conducted on both eyes during a 24-h period, including immediately before and after sleeping. RESULTS: There were no significant differences in any measured variable between right and left eyes [Repeated measurement analysis of variance (Re-ANOVA), p > 0.05]. Diurnal variations (Re-ANOVA, p = 0.001) of CCT, IOPg, IOPcc, and CRF were found during the 24-h period. Significant increases occurred a few minutes after overnight sleep compared with the baseline values at 10:00 PM before sleep (post hoc tests, p = 0.001). However, there were no differences of CH over time during the study period (Re-ANOVA, p = 0.11). A few minutes after awakening, the increase of CCT was not related to the changes of CH, IOPg, IOPcc, or CRF. However, the increase of CRF was significantly correlated with the changes of IOPg. CONCLUSION: Diurnal variation of CH was not detectable in healthy Asian eyes. The diurnal fluctuation of IOP appears not to be associated with CH. However, CRF was increased a few minutes after sleeping, a change that was correlated to the changes of IOPg.

Central corneal thickness and corneal hysteresis during corneal swelling induced by contact lens wear with eye closure.

PURPOSE: To determine if corneal hysteresis (CH) was associated with increased central corneal thickness (CCT) induced by wearing soft contact lenses during eye closure. DESIGN: A prospective laboratory investigation. METHODS: CCT was measured with a modified optical coherence tomography (OCT), and CH was measured with a Reichert Ocular Response Analyzer (ORA) [Reichert Ophthalmic Instruments, Depew, New York, USA]. The ORA also determined values for intraocular pressure (IOP), corneal compensated IOP (IOPcc), and corneal resistance factor (CRF). One randomly selected eye of 20 non-contact lens wearers (four males and 16 females, age 19.7 +/- 1.1 years) was patched during three hours of soft contact lens wear. Measurements were made before lens insertion, immediately upon removal, and every 20 minutes thereafter for 100 minutes. RESULTS: Immediately after contact lens removal, CCT was increased by 13.1 +/- 2.2% (mean +/- SD) compared with baseline (post hoc, P = .001). After 100 minutes, it remained elevated by 2.4 +/- 1.6% (post hoc, P = .001). However, there were no significant differences of CH at any time after lens wear (analysis of variance [ANOVA], P = .9). Immediately after lens removal, there were significant increases in IOP (post hoc, P = .003) and corneal resistance factor (CRF) (post-hoc, P = .015), but not in IOPcc (post hoc, P = .07). After lens wear, there were significant but weak correlations between the percentage change of CCT (CCT%) and IOP (r = 0.32, P = .001) and IOPcc (r = 0.29, P = .001). However, there was no significant correlation between CCT% and CH (r = 0.07, P = .458). CONCLUSION: CH as measured by ORA was not associated with corneal swelling induced by soft contact lens wear in this study group.