Early regional changes in retina and choroid of chicks following monocular hemifield form deprivation.

To investigate regional changes in the chick retina and choroid after hemifield form deprivation (HFD). Ten chicks were randomly and equally divided into a temporal retinal deprivation (TRD) and nasal retinal deprivation (NRD) group. HFD was induced with half-lateral translucent plastic goggles in the right eye; the left eye was kept untreated. Swept-source optical coherence tomography (SS-OCT) images obtained at 0, 3, and 72 hours (h) were analyzed using customized software. After 72 h of TRD, the retinal thickness (RT) of the treated eyes was significantly less than that of the fellow eyes in the temporal (P = 0.034) rather than the nasal (P = 0.083) region. In the NRD group, the RT of the treated eyes was thinner in both the nasal and temporal regions than that of the fellow eyes (P < 0.01). The RT alterations were more pronounced in the temporal (Δ = -16.86 ± 7.14 µm) than in the nasal (Δ = -13.44 ± 4.83 µm) region after 72-h TRD (P = 0.036), whereas the opposite was observed in the NRD group (P = 0.008). The choroidal thickness (ChT) of the treated eyes was less in both the nasal and temporal regions than that of the fellow eyes in both groups after 72-h treatment (P < 0.01). The ChT alterations were more pronounced in the temporal (Δ = -2.48 ± 8.95 µm) than in the nasal (Δ = 23.65 ± 13.58 µm) region after 72-h TRD (P = 0.021), whereas the NRD group showed the opposite effect (P = 0.019). HFD in chicks can lead to retinal and choroidal thinning in the corresponding regions.

Comparison of long-term changes in the effective optical zone following SMILE and FS-LASIK for moderate and high myopia.

BACKGROUND: Visual quality after corneal refractive surgery is linked to the postoperative effective optical zone (EOZ). This study aims to compare long-term changes in the EOZ following small incision lenticule extraction (SMILE) and femtosecond laser-assisted in-situ keratomileusis (FS-LASIK) for moderate and high myopia. METHODS: This study included 42 patients (72 eyes) who underwent either SMILE (36 eyes) or FS-LASIK (36 eyes). A custom software program based on the tangential curvature difference map of the Pentacam HR (Oculus Optikgeräte GmbH) was used to define the EOZ at 3 and 7 years postoperatively. The EOZ, its chronological changes compared to the programmed optical zone (POZ), and the corneal wavefront aberrations following SMILE and FS-LASIK were analyzed. Correlations between the EOZ changes and relevant parameters were evaluated. RESULTS: Three years postoperatively, EOZ following SMILE and FS-LASIK were 5.13 ± 0.27 mm and 4.70 ± 0.24 mm (P < 0.001), respectively. Seven years postoperatively, EOZ following SMILE and FS-LASIK decreased to 5.03 ± 0.28 mm and 4.63 ± 0.23 mm (P < 0.001), respectively. At postoperative 7 years, the percentages of EOZ/POZ were negatively correlated with Q-value changes (ß = -5.120, P = 0.009) following SMILE and positively correlated with the cylinder correction (ß = 1.184, P = 0.004) following FS-LASIK. The induced spherical aberrations in the SMILE group were less than those in the FS-LASIK group (P < 0.05) and were negatively correlated with the EOZ/POZ (ß = -16.653, P < 0.001). CONCLUSIONS: The EOZ following SMILE was larger than that following FS-LASIK in the long postoperative term for moderate and high myopia. Furthermore, a continual reduction in the EOZ was noted after both surgical modalities.

Defocus-induced spatial changes in choroidal thickness of chicks observed by wide-field swept-source OCT.

Choroid has been claimed to be of importance during ocular development. However, how the choroid responds spatially to different visual cues has not been fully understood. The aim of this study was to investigate defocus-induced spatial changes in choroidal thickness (ChT) in chicks. Eight 10-day-old chicks were fitted monocularly with -10 D or +10 D lenses (day 0), which were removed seven days later (day 7). The ChT was measured on days 0, 7, 14, and 21 using wide-field swept-source optical coherence tomography (SS-OCT) and analyzed with custom-made software. Comparisons of the ChT in the central (1 mm), paracentral (1-3 mm), and peripheral (3-6 mm) ring areas and the ChT in the superior, inferior, nasal, and temporal regions were conducted. Axial lengths and refractions were also evaluated. In the negative lens group, the global ChT of the treated eyes was significantly less than that of the fellow eyes on day 7 (interocular difference: 179.28 ± 25.94 µm, P = 0.001), but thicker on day 21 (interocular difference: 241.80 ± 57.13 µm, P = 0.024). These changes were more pronounced in the central choroid. The superior-temporal choroid changed more during induction but less during recovery. In the positive lens group, the ChT of both eyes increased on day 7 and decreased on day 21, with most changes occurring in the central region, too. The inferior-nasal choroid of the treated eyes changed more during induction but less during recovery. These results provide evidence for regionally asymmetric characteristics of the choroidal response to visual cues and insights into the underlying mechanisms of emmetropization.

A novel variant in the keratin 12 gene in a four-generation Chinese family with high myopia.

BACKGROUND: High myopia is a major cause of visual impairment, and genetic factors play crucial roles in the pathogenesis. We performed this study to identify candidate genes for the development of high myopia in a four-generation Chinese family with myopia. METHODS: All family members with myopia and 100 healthy participants were included in this study. Data were obtained on demographics, disease history, and ocular examination results. We performed whole exome sequencing of the genomic DNA and Sanger sequencing to verify the variants. Functional analyses of the variant were performed using software programmes. RESULTS: Nine of thirteen family members were found to have high myopia, amongst which two members were also diagnosed keratoconus. A missense variant in the keratin 12 gene (KRT12, p.Val410Gly) was detected in all high myopia cases but not in other family members without high myopia or the controls. The variant was predicted to be benign by online software programmes. However, modelling of the three-dimensional structure of the protein clearly revealed conformational changes caused by the mutation. CONCLUSIONS: A missense mutation in the KRT12 gene was identified in this Chinese family, which may be associated with the pathogenesis of high myopia.

Variants in the ZNF469 gene in families with Brittle cornea syndrome and keratoconus.

Background: Brittle cornea syndrome 1 (BCS1) is a rare autosomal recessive disorder characterized by corneal and sclera thinning and fragility that is caused by zinc finger protein 469 (ZNF469) gene mutation. Keratoconus is another disease related to corneal thinning. Several reports have linked ZNF469 variants and keratoconus. We recruited a four-generation BCS1 family and two keratoconus families to explore pathogenic ZNF469 variants. Methods: This study included 11 members from a family with BCS1, 2 families with keratoconus, 368 sporadic keratoconus patients and 325 unrelated healthy controls. Whole exome sequencing of DNA from peripheral blood and cross species conservation analysis was used to investigate and verify ZNF469 variants. Results: A new homozygous frameshift mutation c. 6727del (p.Asp2243Thr fs*8) in ZNF469 was detected in the BSC1 family. Two ZNF469 heterozygous variants g.88494671G > A (c.793G > A, p.G265S, rs754776767) were detected in keratoconus family 1 and a heterozygous missense variant g.88498262G > A (c.4384G > A, p.D1462 N, rs577890057) was found in keratoconus family 2. Based on the American College of Medical Genetics and Genomics guidelines, rs577890057 and rs754776767 were predicted to be variants of uncertain significance. c. 6727del (p. Asp2243Thr fs*8) in ZNF469 was identified to be pathogenic. Conclusions: We identified a new homozygous frameshift mutation and two heterozygous missense variations in ZNF469 in the three families. Our findings extend the spectrum of ZNF469 variants associated with keratoconus.

Genetic investigation in a four-generation Chinese family with congenital fibrosis of extraocular muscles and keratoconus.

Here, we have reported the genetic and clinical characteristics of four generations of a family patient from China with congenital fibrosis of extraocular muscles 1 (CFEOM1) and keratoconus (KC). The history of diseases, clinical observations, and blood samples of all family members were collected. A total of 100 healthy participants were recruited as normal controls. The whole exome sequencing of the genomic DNA and polymerase chain reaction were performed on samples obtained from the controls and their family members to verify the gene variants. The functional analyses of the variants were performed by using different software. Two single nucleotide polymorphisms were detected in the proband and other patients in his families, including a heterozygous missense variation, g.39726207C > T (c.2860C > T, p.R954W, rs121912585), in the third highly conserved coiled-coil domain of KIF21A, and a heterozygous missense variant, g.30664732A > C (c.136A > C, p.S46R, rs200111443) in TGFBR2. The variant p.R954W in KIF21A was predicted to be pathogenic using software, whereas p.S46R in TGFBR2 was predicted to be of uncertain significance (VUS). Thus, KC might have occurred in the proband and his daughter because of a combination of genetic mutations and involuntary eye rubbing induced by CFEOM1. This is the first case of concomitant KC in a family having CFEOM1. Thus, the study provides new information about patients with KC having CFEOM1. Furthermore, the study suggests that attention should be paid to the early detection and diagnosis of KC in patients with CFEOM1.

A genetic investigation in five Chinese families with keratoconus.

Background: This study investigated the genetic characteristics of five Chinese families with keratoconus (KC). Methods: In the five families affected by KC, medical records, clinical observations, and blood samples were collected from all individuals. All KC family members (n = 20) underwent both whole exome sequencing of genomic DNA and Sanger sequencing to confirm the variants. Online software was utilized to analyze all variants, and the online server I-TASSER was employed for in silico predictions of the three-dimensional protein structures of the variants. The newly discovered variants and single nucleotide polymorphisms were further examined in 322 sporadic KC patients. Results: The Pentacam tomographic composite index in those affected first-degree family members of the probands showed a pathological change. Five new variants were detected in the five probands and other affected members in their families: a heterozygous missense variant g.19043832C>T (p.Ser145Asn) in the homer scaffolding protein 3 (HOMER3) gene; a heterozygous missense variant g.99452113G>A (p.Gly483Arg) in the insulin-like growth factor 1 receptor (IGF1R) gene; a heterozygous missense variant g.55118280G>T (p.Trp843Leu) in the echinoderm microtubule-associated protein like 6 (EML6) gene; a heterozygous frameshift variant c. 1226_1227del (p.Gln410Glufs*17) in the DOP1 leucine zipper-like protein B (DOP1B) gene; and a heterozygous splice-site variant c.7776+2T>A in the neurobeachin-like protein 2 (NBEAL2) gene. These variations were predicted to be potentially pathogenic and associated with KC. Conclusion: Five novel variants in HOMER3, IGF1R, EML6, DOP1B, and NBEAL2 genes were identified in this study and may be associated with the pathogenesis of KC. This study provides new information about the gene variants and their protein changes in KC patients. The findings should be explored further and could potentially be applied to the early diagnosis of KC before clinical onset.