miR-92b-3p protects retinal tissues against DNA damage and apoptosis by targeting BTG2 in experimental myopia.

BACKGROUND: Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and apoptosis in retinal tissues of negative lens-induced myopic (LIM) guinea pigs by targeting BTG2. METHODS: Biometric measurements of ocular parameters, flash electroretinogram (FERG), and retinal thickness (RT) were performed after miR-92b-3p intravitreal injection in LIM guinea pigs. The apoptotic rate was detected by Annexin V-FITC/PI double staining, and the change in mitochondrial membrane potential was measured by JC-1 staining. Retinal apoptosis and expression of p53, BTG2, and CDK2 were explored by TdT-mediated dUTP-biotin nick labeling (TUNEL) and immunofluorescence staining assays, respectively. BTG2 and its upstream and downstream molecules at gene and protein levels in retinal tissues were measured by real-time quantitative PCR (qPCR) and Western blotting. RESULTS: Compared with normal controls (NC), the ocular axial length of LIM guinea pig significantly increased, whereas refraction decreased. Meanwhile, dMax-a and -b wave amplitudes of ERG declined, retinal thickness was decreased, the number of apoptotic cells and apoptotic rate in LIM eyes was exaggerated, and the mitochondrial membrane potential significantly decreased. In addition, results of qPCR and Western blot assays showed that the expression levels of p53, BTG2, CDK2, and BAX in LIM guinea pigs were higher than the levels of the NC group, whereas the BCL-2 expression level was decreased. By contrast, the miR-92b-3p intravitreal injection in LIM guinea pigs could significantly inhibit axial elongation, alleviate DNA damage and apoptosis, and thus protect guinea pigs against myopia. CONCLUSION: In conclusion, p53 and BTG2 were activated in the retinal tissue of myopic guinea pigs, and the activated BTG2 could elevate the expression of CDK2 and BAX, and attenuate the expression of BCL-2, which in turn promote apoptosis and eventually lead to retinal thinning and impaired visual function in myopic guinea pigs. The miR-92b-3p intravitreal injection can attenuate the elongation of ocular length and retinal thickness, and inhibit the CDK2, BAX, and p53 expression by targeting BTG2, thereby ameliorating DNA damage and apoptosis in LIM guinea pigs and protecting ocular tissues.

The landscape of angiogenesis and inflammatory factors in eyes with myopic choroidal neovascularization before and after anti-VEGF injection.

INTRODUCTION: To investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. METHODS: Aqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. RESULTS: In this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. CONCLUSION: Our findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C's correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.

Associations between corneal curvature and other anterior segment biometrics in young myopic adults.

To investigate the associations between corneal curvature (CC) and other anterior segment biometrics in young myopic adults. In this retrospective multi-center study, 7893 young myopic adults were included. CC and other anterior segment biometrics were measured by Scheimpflug imaging (Pentacam). CC was defined as SimK at central 3 mm area, and other anterior segment biometrics included white-to-white corneal diameter (WTW), central corneal thickness (CCT), corneal volume (CV) at 3 mm, 5 mm, and 7 mm area, anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), anterior corneal eccentricity (ACE) and asphericity (ACAP), posterior corneal eccentricity (PCE) and asphericity (PCAP), anterior chamber depth (ACD), and anterior chamber volume (ACV). Univariate regression analyses were used to assess the associations between CC and other anterior segment biometrics, and multivariate regression analyses were further performed to adjusted for age, gender and spherical equivalent. CC was higher in patients of female gender and higher myopia (all P < 0.05). Eyes in higher CC quartiles had lower WTW, thinner CCT, lower CV at 3 mm and 5 mm, lower ACD, and lower ACV (all P < 0.001), but had larger ACA, larger PCA, less PCE and less PCAP (all P < 0.001), compared to eyes in lower CC quartiles. The trends of CV at 7 mm, ACE and ACAP were inconsistent in different CC quartiles. After adjusting for age, gender and spherical equivalent with multivariate linear regression, CC was positively correlated to CV at 7 mm (ßs = 0.069), ACA (ßs = 0.194), PCA (ßs = 0.187), ACE (ßs = 0.072), PCAP (ßs = 0.087), and ACD (ßs = 0.027) (all P < 0.05), but was negatively correlated to WTW (ßs = - 0.432), CCT (ßs = - 0.087), CV-3 mm (ßs = - 0.066), ACAP (ßs = - 0.043), PCE (ßs = - 0.062), and ACV (ßs = - 0.188) (all P < 0.05). CC was associated with most of the other anterior segment biometrics in young myopic adults. These associations are important for better understanding of the interactions between different anterior segment structures in young myopic patients, and are also useful for the exploration of the pathogenesis of myopia.

3D printed fibroblast-loaded hydrogel for scleral remodeling to prevent the progression of myopia.

Pathologic myopia has seriously jeopardized the visual health of adolescents in the past decades. The progression of high myopia is associated with a decrease in collagen aggregation and thinning of the sclera, which ultimately leads to longer eye axis length and image formation in front of the retina. Herein, we report a fibroblast-loaded hydrogel as a posterior scleral reinforcement (PSR) surgery implant for the prevention of myopia progression. The fibroblast-loaded gelatin methacrylate (GelMA)-poly(ethylene glycol) diacrylate (PEGDA) hydrogel was prepared through bioprinting with digital light processing (DLP). The introduction of the PEGDA component endowed the GelMA-PEGDA hydrogel with a high compression modulus for PRS surgery. The encapsulated fibroblasts could consistently maintain a high survival rate during 7 days of in vitro incubation, and could normally secrete collagen type I. Eventually, both the hydrogel and fibroblast-loaded hydrogel demonstrated an effective shortening of the myopic eye axis length in a guinea pig model of visual deprivation over three weeks after implantation, and the sclera thickness of myopic guinea pigs became significantly thicker after 4 weeks, verifying the success of sclera remodeling and showing that myopic progression was effectively controlled. In particular, the fibroblast-loaded hydrogel demonstrated the best therapeutic effect through the synergistic effect of cell therapy and PSR surgery.

Association between inflammatory cytokines and oxidative stress levels in aqueous humor with axial length in human myopia.

This study investigated the content of inflammatory cytokines and oxidative stress levels in the aqueous humor (AH) of patients with high myopia (HM) and explored the relationship between these factors and the axial length (AL) of the eye, to explore the roles of mild intraocular inflammation and oxidative stress imbalance in the occurrence and development of myopia. AH samples from 40 patients (70 eyes) were collected during implantable collamer lens (ICL-V4c) surgery. The subjects were divided into three groups according to AL: group A (AL ≤ 26 mm), group B (26 < AL ≤ 28 mm), and group C (AL ≥ 28 mm). The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), and interleukin-1ß (IL-1ß) in the AH of the three groups were measured using the Luminex system. Oxidative stress levels were measured using reagent kits targeting total antioxidant capacity (T-AOC), catalase (CAT), and nitric oxide (NO) and malonaldehyde (MDA) content. The results showed compared with group A, IL-1ß, MMP-2, and IL-6 concentrations were significantly higher and T-AOC levels were significantly lower in group C. There were no significant differences in CAT, NO, MDA, or TNF-α levels among the groups. The concentrations of IL-6 (r = 0.379, p = 0.016), MMP-2 (r = 0.469, p = 0.002), and MDA (r = 0.354, p = 0.025) in AH were positively correlated with the AL, whereas T-AOC (r = -0.678, p = 0.000) was negatively correlated with AL. These results suggest that mild intraocular inflammation and oxidative stress imbalance may be associated with myopia. Further experiments are needed to confirm the role of mild intraocular inflammation and oxidative stress imbalance in the occurrence and development of myopia.

Pathogenesis of myopic choroidal neovascularization: A systematic review and meta-analysis.

Myopic choroidal neovascularization (CNV) is a vision-threatening complication of high myopia. Here, we systematically review cohort, case-control, and cross-sectional studies in PubMed, Embase, and Web of Science, and summarize the associated factors of myopic CNV using meta-analysis where applicable. Among 1,333 records assessed, 50 were found eligible, all having a low-to-moderate risk of bias. Highly myopic eyes with CNV had a higher risk of lacquer cracks (odds ratio = 2.88) and patchy chorioretinal atrophy (odds ratio = 3.43) than those without. The mean posterior staphyloma height (µm) was greater in myopic CNV eyes than in highly myopic eyes without CNV (mean difference = 82.03). The thinning of choroidal thickness (µm) between myopic eyes with and without CNV differed significantly (mean difference = -47.76). The level of vascular endothelial growth factor (pg/ml) in the aqueous humor of myopic CNV eyes was significantly higher than in highly myopic eyes without CNV (mean difference = 24.98), the same as interleukin-8 (IL-8) (pg/ml, mean difference = 7.73). Single-nucleotide polymorphisms in the vascular endothelial growth factor, complement factor I, and collagen type VIII alpha 1 genes were associated with myopic CNV. We found that myopic CNV eyes have a higher ratio of lacquer cracks and patchy chorioretinal atrophy, thinner choroid, greater posterior staphyloma height, and a higher level of vascular endothelial growth factor and IL-8 in aqueous. Structural predisposing lesions, hemodynamic, genetic, and systemic factors are also associated with myopic CNV.

Myopic Versus Glaucomatous Parapapillary Beta Zone in Myopic Eyes Versus Eyes With Secondary Angle-Closure Glaucoma.

Purpose: To search for histologic differences in the beta zone between myopic eyes versus eyes with secondary angle-closure glaucoma. Methods: The histomorphometric study consisted of human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma. Results: The study included 100 eyes (age: 62.1 ± 15.1 years; axial length: 25.6 ± 3.1 mm; range: 20.0-35.0 mm). In non-highly myopic glaucomatous eyes compared with non-highly myopic nonglaucomatous eyes, the parapapillary alpha zone was longer (223 ± 168 µm vs. 125 ± 128 µm; P = 0.03), beta zone prevalence (15/20 vs. 6/41; P < 0.001) and length (277 ± 245 µm vs. 44 ± 150 µm; P = 0.001) were higher, and RPE cell density in the alpha zone and alpha zone border was lower (all P < 0.05). In highly myopic nonglaucomatous eyes compared with non-highly myopic glaucomatous eyes, parapapillary RPE drusen prevalence (2/19 vs. 10/10; P = 0.01) and alpha zone prevalence (2/19 vs. 16/20; P < 0.001) and length (23 ± 68 µm vs. 223 ± 168 µm; P < 0.001) were lower. In non-highly myopic glaucomatous eyes, Bruch's membrane (BM) thickness decreased (P < 0.001) from the beta zone (6.0 ± 3.1 µm) to the alpha zone (5.1 ± 4.3 µm) and peripheral to it (3.0 ± 0.9 µm). In highly myopic nonglaucomatous eyes, BM thickness did not differ (P > 0.10) between all three regions. In the total study population, RPE cell density in the alpha zone (24.5 ± 9.3 cells/240 µm) was higher than at the alpha zone border (19.2 ± 4.8 cells/240 µm; P < 0.001) or peripheral to it (19.0 ± 3.6 cells/240 µm; P < 0.001). Conclusions: The glaucomatous beta zone in eyes with chronic angle-closure glaucoma (with the alpha zone, parapapillary RPE drusen, thickened BM, and higher RPE cell count in the adjacent alpha zone) differs histologically from the myopic beta zone (characterized by the absence of the alpha zone and parapapillary RPE drusen, unremarkable BM thickness, and unremarkable parapapillary RPE). The differences suggest different etiologies of the glaucomatous versus myopic beta zone.

Longitudinal Changes of Bruch's Membrane Opening, Anterior Scleral Canal Opening, and Border Tissue in Experimental Juvenile High Myopia.

Purpose: To investigate the relative positional changes between the Bruch's membrane opening (BMO) and the anterior scleral canal opening (ASCO), and border tissue configuration changes during experimental high myopia development in juvenile tree shrews. Methods: Juvenile tree shrews were assigned randomly to two groups: binocular normal vision (n = 9) and monocular -10 D lens treatment starting at 24 days of visual experience to induce high myopia in one eye while the other eye served as control (n = 12). Refractive and biometric measurements were obtained daily, and 48 radial optical coherence tomography B-scans through the center of the optic nerve head were obtained weekly for 6 weeks. ASCO and BMO were segmented manually after nonlinear distortion correction. Results: Lens-treated eyes developed high degree of axial myopia (-9.76 ± 1.19 D), significantly different (P < 0.001) from normal (0.34 ± 0.97 D) and control eyes (0.39 ± 0.88 D). ASCO-BMO centroid offset gradually increased and became significantly larger in the experimental high myopia group compared with normal and control eyes (P < 0.0001) with an inferonasal directional preference. The border tissue showed a significantly higher tendency of change from internally to externally oblique configuration in the experimental high myopic eyes in four sectors: nasal, inferonasal, inferior, and inferotemporal (P < 0.005). Conclusions: During experimental high myopia development, progressive relative deformations of ASCO and BMO occur simultaneously with changes in border tissue configuration from internally to externally oblique in sectors that are close to the posterior pole (nasal in tree shrews). These asymmetric changes may contribute to pathologic optic nerve head remodeling and an increased risk of glaucoma later in life.

Development and validation of an intuitive biomechanics-based method for intraocular pressure measurement: a modal analysis approach.

BACKGROUND: Current intraocular pressure (IOP) measurements based on non-contact tonometry are derived from statistics-driven equations and lack biomechanical significance, which often leads to under-estimation in post-refractive surgery cornea. This study aims to introduce and validate modal analysis-derived intraocular pressure (mIOP) as a novel method generated through Legendre-based modal decomposition of the anterior corneal contour; it provides an accurate and intuitive IOP measurement from an energy-based perspective. METHODS: This retrospective study included 680 patients. Healthy participants were divided into reference (n = 385) and validation (n = 142) datasets, and the others underwent either femtosecond-assisted laser in situ keratomileusis (FS-LASIK, n = 58) or transepithelial photorefractive keratectomy (TPRK, n = 55). Corneal curvature of the right eyes was extracted from raw serial cross-sectional images of the cornea generated by Corvis ST, a noncontact tonometer with a high-speed Scheimpflug-camera. Legendre expansion was then applied to the corneal curvature to obtain the modal profiles (i.e., temporal changes of the coefficient for each basis polynomial [modes]). Using the reference dataset, feature selection on the modal profiles generated a final mIOP model consisting of a single parameter: total area under curve (frames 1-140) divided by the area under curve of the rising phase (frames 24-40) in the fourth mode, i.e. the M4 ratio. Validation was performed in both the healthy validation and postoperative datasets. IOP-Corvis, pachymetry-corrected IOP, biomechanically corrected IOP, and mIOP values were compared. For the FS-LASIK and TPRK groups, pairwise postoperative IOP changes were analyzed through repeated measures analysis of variance, and agreement was examined through Bland-Altman analysis. Using a finite element analysis based three-dimensional model of the human cornea, we further compared the M4 ratio with the true intraocular pressure within the physiological range. RESULTS: The M4 ratio-based mIOP demonstrated weak to negligible association with age, radius of corneal curvature, and central corneal thickness (CCT) in all validation analyses, and performed comparably with biomechanically corrected IOP (bIOP) in the refractive surgery groups. Both remained nearly constant postoperatively and were not influenced by CCT changes. Additionally, M4 ratio accurately represented true intraocular pressure in the in silico model. CONCLUSIONS: mIOP is a reliable IOP measurement in healthy and postrefractive surgery populations. This energy-based, ratio-derived approach effectively filters out pathological, rotational, misaligned movements and serves as an interpatient self-calibration index. Modal analysis of corneal deformation dynamics provides novel insights into regional corneal responses against pressure loading.

KCTD1 and Scalp-Ear-Nipple ('Finlay-Marks') syndrome may be associated with myopia and Thin basement membrane nephropathy through an effect on the collagen IV α3 and α4 chains.

INTRODUCTION: Scalp-Ear-Nipple syndrome is caused by pathogenic KCTD1 variants and characterised by a scalp defect, prominent ears, and rudimentary breasts. We describe here further clinical associations in the eye and kidney. METHODS: Fifteen affected members from two unrelated families with p.(Ala30Glu) or p.(Pro31Leu) in KCTD1 were examined for ocular and renal abnormalities. The relevant proteins were studied in the eye and kidney, and the mutation consequences determined from mouse knockout models. RESULTS: Five males and 10 females with a median age of 40 years (range 1-70) with pathogenic variants p.(Ala30Glu) (n = 12) or p.(Pro31Leu) (n = 3) in KCTD1 were studied. Of the 6 who underwent detailed ophthalmic examination, 5 (83%) had low myopic astigmatism, the mean spherical equivalent of 10 eyes was 2.38D, and one (17%) had hypermetropic astigmatism. One female had a divergent strabismus.Five individuals had renal cysts (5/15, 33%), with renal biopsy in one demonstrating a thinned glomerular basement membrane identical to that seen in Thin basement membrane nephropathy (AD Alport syndrome).In the eye, KCTD1 and its downstream targets, TFAP2, and the collagen IV α3 and α4 chains localised to the cornea and near the retinal amacrine cells. In the kidney, all these proteins except TFAP2 were expressed in the podocytes and distal tubules. TFAP2B and COL4A4 knockout mice also had kidney cysts, and COL4A3 and COL4A4 knockout mice had myopia. CONCLUSION: Individuals with a pathogenic KCTD1 variant may have low myopic astigmatism and represent a further rare genetic cause for a thinned glomerular basement membrane.

Enhanced Apoptosis in Choroidal Tissues in Lens-Induced Myopia Guinea Pigs by Activating the RASA1 Signaling Pathway.

Purpose: This study aimed to explore the role of the RAS p21 protein activator 1 (RASA1) signaling pathway in apoptosis in choroid tissues from guinea pigs with negative lens-induced myopia (LIM). Methods: Biometric measurements were performed to examine refractive status, ocular parameters, and choroidal thickness (ChT) after myopia induction. The choroidal morphology was observed by hematoxylin and eosin (H&E) staining and TUNEL assay. The expression of the RASA1 signaling pathway at the mRNA and protein levels in choroidal tissues was measured by real-time quantitative PCR (qPCR) and western blot assays. Results: Compared with the normal control (NC) group, the ocular length of the guinea pigs in LIM increased remarkably, as did the myopic refraction. ChT decreased after myopia induction. H&E staining showed that the thickness and laxity of the choroidal tissues in LIM were strikingly reduced. The number of apoptotic cells in the LIM eyes was increased. Moreover, qPCR and western blot assays showed that the expression levels of both RASA1 and BCL-2-associated agonist of cell death (BAD) were higher in the LIM group than in the NC group, whereas the expression level of B-cell lymphoma 2 (BCL-2) was decreased after 2 weeks of experimental myopia. However, the trend of RASA1, BAD, and BCL-2 expression was reversed after 4 weeks of experimental myopia compared with levels after 2 weeks of experimental myopia. Conclusions: Results showed that the RASA1 signaling pathway is activated in choroid tissues in myopic guinea pigs. Activated RASA1 signaling induces high BAD expression and low BCL-2 expression, which in turn promotes apoptosis and ultimately causes ChT thinning in myopic guinea pigs.

Un estudio de prevalencia de error de refracción en niños entrecerrados (6-12 años) asistiendo al Hospital Dr. Aso-Eye Shahed / A study of Prevalence of Refractive Error in Squinted children (6-12 years) attending shahed Dr. Aso-Eye Hospital

Determinar la prevalencia del error de refracción (RE) como causa en los ojos en los niños en niños de esta edad (6-12 años) en la ciudad de Sulaimania. El estudio de tasa de prevalencia entre los pacientes que asisten al Shahed Dr. Aso Eye Hospital para el período del 1 de octubre de 2008 al 1 de junio de 2009. Un total de 116 niños (6-12 años) asisten al departamento de entrecerrares durante aproximadamente 8 meses. El estudio incluyó ambos sexos, eran niños de 55 años y niñas 61. Se sometieron a un examen ocular completo. Encontramos que (72) pacientes (62.02 %) tenían un error de refracción, incluyen: 33 pacientes (45.9 %) = hipermetropia (H); 22 pacientes (29.16%) = miopía [m]; 18 pacientes (24.3%) astigmatismo (AST.); 4 mixtos; 6 h-as. y 8 m-as. En conclusiones, la causa más frecuente del entrecerrar de la infancia a este ancho [6-12 años) es el error refractivo, mientras que las otras causas en su conjunto constituyen solo 1/3 de las causas, y el error de refracción más común es la hipermetropía

To determine the prevalence of refractive error (RE) as a cause in squinted in children in this aged (6-12 years) in Sulaimania city. The prevalence rate study among patient attending Shahed Dr. Aso eye hospital for the period from 1st October 2008 - 1st June 2009. A total of 116 children ( 6-12 years) attending squint department for about 8 months. The study included both sexes, were boys 55 and girls 61. Underwent full ocular examination. We found that (72) patients (62.02%) had refractive error, include: 33 patients (45.9 %) = Hypermetropia (H); 22 patients (29.16%) = Myopia [M]; 18 patients (24.3%) Astigmatism (Ast.); 4 mixed; 6 H-Ast. and 8 M-Ast. In conclusions, the most prevalent cause of childhood squint at this aged [6-12 years) is refractive error while the other causes as a whole constitute only 1/3 of the causes, and most common refractive error is hypermetropia

Effect of TGF-ß2 on the Mechanical Properties of Posterior Scleral Fibroblasts in Experimental Myopia.

Objective: The effects of TGF-ß2 on mechanical properties of sclerotic desmocytes isolated from healthy and myopic guinea pigs were investigated in order to further understand the pathogenesis of myopia. To study the effect of TGF-ß2 on the mechanical properties of posterior scleral fibroblasts in experimental myopia. Methods: A lens-induced myopia (LIM) animal model was developed in 12 guinea pigs, with the opposite eye serving as a self-control (SC). Five untreated guinea pigs served as normal controls. Lenses were removed 30 days after model onset. Primary scleral fibroblasts were isolated and passaged twice and then treated with vehicle control or 1, 10, or 100 ng/mL TGF-ß2. After 24 h, micropipette aspiration was used to investigate the viscoelastic properties of the cells. Results: Scleral fibroblasts from LIM exhibited significantly higher equilibrium moduli and apparent viscosities relative to SC without TGF-ß2 treatment. Treatment of LIM or SC scleral fibroblasts with 1 or 10 ng/mL TGF-ß2 led to significantly different (p < 0.05) equilibrium moduli and apparent viscosities compared with vehicle control, whereas no significant differences were observed upon treatment with 100 ng/mL TGF-ß2. LIM cells treated with 1 and 10 ng/mL TGF-ß2 exhibited lower equilibrium moduli and apparent viscosities compared with similarly treated SC cells, but LIM cells and SC cells treated with 100 ng/mL TGF-ß2 had similar mechanical properties. Conclusions: The addition of 1 and 10 ng/mL TGF-ß2 can lower the equilibrium modulus and apparent viscosity of scleral fibroblasts in the normal eye.

Fresh Human Myopic Lenticule Intrastromal Implantation for Keratoconus Using SMILE Surgery in a Long-term Follow-up Study: Ultrastructural Analysis by Transmission Electron Microscopy.

PURPOSE: To investigate new intrastromal histological structures that develop after myopic human lenticular implantation in keratoconus with femtosecond laser-assisted small incision lenticule extraction (SMILE) surgery using transmission electron microscopy. METHODS: Sixty eyes with advanced keratoconus indicated for corneal transplantation were included in this study. Fresh myopic lenticular implants were placed in all eyes through SMILE surgery. Lenticular implants were extracted from patients with myopic refractive errors of the cornea, untreated keratoconus, and treated keratoconus following 1, 2, and 3 years of surgery. These five lenticular samples were examined under the electron microscope and compared. RESULTS: Disorganized and thinned collagen fibers were observed in the stroma with degenerative stromal cells (telocyte-like cells and keratocytes) in the keratoconic cornea. Apoptotic bodies and cell debris were easily observed near the disorganized fibers. In contrast, the myopic refractive error of the control and treatment groups demonstrated well-organized parallel lamellar structures. Healthy keratocytes and telocyte-like cells were observed in samples obtained 1, 2, and 3 years after lenticular implantation. Thus, telocyte-like cells may be activated by appropriate stimuli, such as stem cells, and be involved in stromal regeneration. CONCLUSIONS: Fresh myopic intrastromal lenticular implantation is a safe, economical, and reliable technique that leads to increased corneal thickness, improved visual acuity, and the regeneration of healthy keratocytes and telocyte-like cells that are involved in stromal regeneration. [J Refract Surg. 2022;38(8):520-528.].

Swept source OCT-Angiography assessing a case of aneurysmal type 1 neovascularization secondary to high-myopic posterior staphyloma.

AIM: To report an uncommon case of aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy) secondary to high-myopic staphyloma in a Caucasian patient, assessed with multimodal imaging including swept source OCT-Angiography. METHODS: Observational case report. RESULTS: About 73-year-old Caucasian male patient with high myopia (axial length = 27.24 mm). Fundus examination showed a myopic conus and a deep orange-brownish nodular lesion at the edge of a deep haemorrhage and connected to a large choroidal vessel. ICGA showed a circular hyperfluorescent lesion in mid-phase, without any branching vascular network. OCT-Angiography could detect the aneurysmal lesion non-invasively as a small circular high-flow lesion in the outer retina slab, with a shadowing in the choriocapillaris slab. At the level of the aneurysmal lesion, structural OCT showed a high bilobed PED, without any subretinal fluid. A vascular flow was noted within the PED on cross-sectional OCT-A, confirming the vascular aneurysmal nature of this lesion. Additionally, swept source OCT highlighted the presence of an abrupt change in choroidal thickness, from 62 µm in the peripapillary area to 120 µm underneath the polypoidal lesion, with dilated choroidal vessels. CONCLUSION: To our knowledge, this is the first report of OCT-A findings in aneurysmal (polypoidal) dilation secondary to high-myopic staphyloma. We could demonstrate the usefulness of OCT-A detecting non-invasively the aneurysmal dilation and the usefulness of swept source OCT assessing the choroidal structure to better understand the pathophysiology of this uncommon finding.

The utility of measures of anterior segment parameters of a Pentacam Scheimpflug tomographer in discriminating high myopic astigmatism from keratoconus.

The study aimed to evaluate and compare anterior segment parameters between keratoconic eyes and eyes with high myopic astigmatism using Pentacam Scheimpflug tomography. This was a retrospective cross-sectional study that included sixty keratoconic eyes (thirty-two persons) and seventy-three eyes (forty-six persons) with high myopic astigmatism with mean ages 24.72 ± 11.65years and 26.60 ± 10.69years, respectively. Twenty-three parameters from the topographic map and fifteen parameters from the Belin-Ambrosió enhanced ectasia display map of the printouts of a Scheimpflug principle-based Pentacam tomographer were evaluated for their diagnostic accuracy using Receiver Operating Characteristic (ROC) curve. All parameters except cornea volume, anterior chamber volume, and anterior chamber angle indicated a significant difference between high myopic astigmatism and keratoconic eyes. The area under the receiver operating characteristic (AUROC) of eighteen Pentacam parameters was excellent (0.9-1.0) in discriminating keratoconus from high myopic astigmatism, out of which four {anterior minimum sagittal curvature (ant. Rmin), posterior minimum sagittal curvature (post. Rmin), maximum Ambrosió relational thickness (ART max) and total deviation value (D)} indicated excellent (>90%) sensitivity and specificity in addition to the excellent AUROC values. Topographic and Belin-Ambrosió enhanced ectasia display (BAD) maps of a Scheimpflug principle-based Pentacam tomographer are useful in enhancing the diagnosis of keratoconus and may also provide valuable information in effectively screening for keratoconus cases among refractive surgery candidates with high myopic astigmatism.

Association between choriocapillaris flow deficit and choroidal neovascularization activity in eyes with myopic choroidal neovascularization.

Although choriocapillaris flow deficit (CFD) around choroidal neovascularization (CNV) is less associated with CNV activity in myopic eyes, no reports are investigating its size as an indicator of CNV activity. We investigated the relationship between CFD and high myopia-related CNV. In this retrospective, observational study, patients underwent optical coherence tomography angiography (OCTA) with split-spectrum amplitude-decorrelation angiography for diagnosing pathological myopic CNV (mCNV); CFD features around CNV margins were evaluated. Of the 33 eyes (30 patients), 11 (33.3%) had active mCNV, and 22 (66.7%) had inactive CNV. Six eyes (18.2%) were treatment-naïve, while the remainder previously underwent anti-vascular endothelial growth factor therapy. On OCTA, blood flow signals were detected in CNV in the outer retinal layer in 28 (84.8%) eyes, including all active cases (11 cases) and 17 (77.3%) of 22 inactive cases. CNV flow signal size correlated significantly with activity (P < 0.001). CFD around CNV was observed in 24 eyes (72.7%), including all active cases (11 cases) and 13 (59.1%) of 22 inactive cases. CFD size correlated significantly with CNV activity (P < 0.001). The size of both the CFD area around CNV and CNV flow signal area are useful indicators of CNV activity in eyes with mCNV, which may help determine treatment timing.

Pupil dynamics after in-the-bag versus anterior and retropupillary iris-fixated intraocular lens implantation.

An Intraocular Lens (IOL) fixated on the iris either anteriorly, as a phakic IOL, or posteriorly, as an aphakic IOL, can influence pupil motility. In this interventional case series study, we evaluated pupil size under different levels of illumination (scotopic = 0.04 lx, low-mesopic = 0.4 lx and high-mesopic = 4 lx) for anterior iris-claw IOL fixation for correcting myopia or hyperopia (IFPH), retropupillary iris-claw IOL fixation to correct aphakia or as treatment for late in-the-bag IOL dislocation/subluxation (IFRP), and capsular-fixation IOL in-the-bag implantation (IB). Pupil size was measured preoperatively for the IFPH- and IB-group as well as 6 months after surgery for all groups. We analyzed a total of 70 eyes: 22 eyes of 11 patients with phakic IOLs, 22 eyes of 20 patients in the IFRP group and 26 eyes of 13 patients in the IB group. Both IFPH and IB showed a smaller postoperative scotopic pupil size, compared with the preoperative values. When compared to postoperative values of IB and IFPH, IFRP showed a significantly smaller postoperative scotopic pupil size (IFPH: 5.89 ± 0.83 mm, IFRP: 4.37 ± 0.83 mm, IB: 5.34 ± 0.98 mm, p < 0.001) while no differences were seen at high-mesopic lighting. Neither of the surgical techniques seems to impair the constriction of the pupil.

Customized eye modeling for optical quality assessment in myopic femto-LASIK surgery.

Refractive surgery is recognized as an effective method for myopia treatment, but it can induce night vision disturbances such as glare. We present an eye modeling method for the optical quality assessment in response to the structural changes in the eyes by femto-LASIK surgery. Customized eye models were built from the measurements of 134 right eyes pre- and post-operatively. Optical performance was evaluated using spot diagrams, point spread functions (PSFs), modulation transfer functions (MTFs), and chromatic aberrations at various fields (0°-30°), different pupil diameters (2-6 mm), and initial myopias (- 1.25 to - 10.5 D). Pupil size and initial myopia are the two major factors that affect visual performance of post-operative eyes. The results of spot diagrams, PSFs, and MTFs indicated that post-operative visual performance deteriorated as the visual field and pupil size increased, and it was significantly influenced by initial myopia. Post-operative chromatic aberrations were also affected by initial myopia. As pupil size increased, the post-operative longitudinal chromatic aberrations tended to decrease slightly, while the transverse chromatic aberrations remained similar. The use of eye modeling for refractive surgery assessment could possibly provide a more personalized surgical approach, could improve the prediction accuracy of refractive surgery outcomes, and promote the invention and development of better surgical methods.

Cystoid maculopathy is a frequent feature of Cohen syndrome-associated retinopathy.

Cohen syndrome (CS) is a rare syndromic form of rod-cone dystrophy. Recent case reports have suggested that cystoid maculopathy (CM) could affect CS patients with an early onset and high prevalence. Our study aims at improving our understanding and management of CM in CS patients through a retrospective case series of ten CS patients with identified pathogenic variants in VPS13B. Longitudinal optical coherence tomography (OCT) imaging was performed and treatment with carbonic anhydrase inhibitors (CAI) was provided to reduce the volume of cystoid spaces. CM affected eight out of ten patients in our cohort. The youngest patient showed a strong progression of macular cysts from the age of 4.5 to 5 years despite oral CAI medication. Other teenage and young adult patients showed stable macular cysts with and without treatment. One patient showed a moderate decrease of cystoid spaces in the absence of treatment at 22 years of age. Through a correlative analysis we found that the volume of cystoid spaces was positively correlated to the thickness of peripheral and macular photoreceptor-related layers. This study suggests that CAI treatments may not suffice to improve CM in CS patients, and that CM may resolve spontaneously during adulthood as photoreceptor dystrophy progresses.