OBJECTIVES: Keratoconus (KC) is a progressive corneal ectasia disorder, arising from a myriad of causes including genetic predispositions, environmental factors, biomechanical influences, and inflammatory reactions. This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population. METHODS: Twenty-five patients with primary KC as well as 50 unrelated population-matched healthy controls, were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population. Sanger sequencing and whole-exome sequencing (WES) were used to analyze mutations in the zinc finger protein 469 (ZNF469) gene. Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis. RESULTS: Five novel heterozygous missense variants were identified in KC patients. Among them, 2 compound heterozygous variants, c.8986G>C (p. E2996Q) with c.11765A>C (p. D3922A), and c.4423C>G (p. L1475V) with c.10633G>A (p. G3545R), were determined to be possible pathogenic factors for KC. CONCLUSIONS Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population. These mutation sites may provide valuable information for future genetic screening of KC patients and their families.
Adolescent ; Adult ; Female ; Humans ; Male ; Case-Control Studies ; China/ethnology* ; Exome Sequencing ; Genetic Predisposition to Disease ; Keratoconus/genetics* ; Mutation ; Mutation, Missense ; Transcription Factors/genetics* ; East Asian People/genetics*

Objectives: This study described the clinical profile of patients with keratoconus at a single tertiary referral hospital. Methods: This was a single-center, retrospective, cross-sectional study that reviewed medical records of patients diagnosed with keratoconus from January 2015 to August 2022. Data on the clinical profile, intervention, and clinical outcomes were collected from the chart review. Results: Forty (40) patients (79 eyes) were included in the study. Majority (98%) had bilateral disease in which 22 (55.5%) were affected asymmetrically. The mean age was 21 years. Most patients (72.5%) were male. Blurring of vision was the chief complaint in all patients. Atopy was present in 23 patients (57.5%). History of vigorous eye rubbing was present in 31 (77.5%). The mean interval from onset of symptoms to consult was 46.4 ± 33.38 months. The mean pinhole corrected distance visual acuity was 0.47 ± 0.41 (Snellen equivalent of 20/59). The average spherical equivalent was -7.48D ± 6.99D. Corneal protrusion on slit-lamp biomicroscopy was seen in 78 eyes (98.7%). Other findings included Fleischer ring (53.2%), Vogt's striae (19.0%), and apical corneal scar (24.0%). Only one eye (1.3%) had no corneal findings. Thirty-nine eyes (49.3%) were classified as advancedsevere keratoconus. Rigid contact lens was planned for 60 eyes (75.9%). Sixty-two eyes (78.5%) were for collagen cross-linking. Deep anterior lamellar keratoplasty was planned in 10 eyes (12.7%) and penetrating keratoplasty in two eyes (2.5%). Conclusion Keratoconus at the Philippine General Hospital was most frequently seen in young males and asymmetrically affects both eyes. Patients consulted relatively late and presented with a more advanced stage of the disease. History of ocular allergy and eye rubbing were significant risk factors. Improving awareness of this condition must be emphasized to detect keratoconus earlier.
Keratoconus ; Cornea ; Demography ; Philippines

PURPOSE: To investigate the long-term results (at least 5 years of follow-up) of the mini asymmetric radial keratotomy (MARK) and corneal cross-linking (CXL) combined intervention, also known as the ‘Rome protocol,’ for patients with progressive stage I and II keratoconus and contact lens intolerance. METHODS: This was a retrospective observational case series. Fifteen eyes of 12 patients were evaluated, with a mean follow-up of 6.9 years. To assess the efficacy and stability of the MARK + CXL combined protocol, best spectacle-corrected visual acuity, mean pachymetry, and mean keratometry were recorded preoperatively and at least 1, 3, and 5 years postoperatively. Statistical analysis was performed using the R platform and involved the Wilcoxon signed-rank and Kruskal-Wallis non-parametric tests. RESULTS: Best spectacle-corrected visual acuity improved for all patients, from 0.46 ± 0.69 logarithm of the minimum angle of resolution (20 / 60) to 0.15 ± 0.69 logarithm of the minimum angle of resolution (20 / 30, p = 0.0006), while mean pachymetry increased in 93% of patients, from 442.80 ± 61.02 to 464.50 ± 62.72 µm (p = 0.003). Lastly, mean keratometry improved in 87% of patients after 6.9 years of observation from 48.82 ± 5.00 to 43.25 ± 3.58 diopters (p = 0.008). No intraoperative or postoperative complications were observed. CONCLUSIONS: The MARK + CXL combined protocol was effective in treating keratoconus by halting corneal thinning and bulging. In addition, this procedure significantly improved visual acuity based on long-term follow-up data. Analysis of data from a larger cohort of patients would be useful to support these findings.
Cohort Studies ; Follow-Up Studies ; Humans ; Keratoconus ; Keratotomy, Radial ; Postoperative Complications ; Retrospective Studies ; Visual Acuity

Study of the mechanical properties of in vivo corneal materials is an important basis for further study of corneal physiological and pathological phenomena by means of finite element method. In this paper, the elastic coefficient ( ) and viscous coefficient ( ) of normal cornea and keratoconus under pulse pressure are calculated by using standard linear solid model with the data provided by corneal visualization scheimpflug technology. The results showed that there was a significant difference of and between normal cornea and keratoconus cornea ( < 0.05). Receiver operating characteristic curve analysis showed that the area under curve (AUC) for , and their combined indicators were 0.776, 0.895 and 0.948, respectively, which indicated that keratoconus could be predicted by and . The results of this study may provide a reference for the early diagnosis of keratoconus and avoid the occurrence of keratoconus after operation, so it has a certain clinical value.
Area Under Curve ; Cornea ; physiology ; Elasticity ; Humans ; Keratoconus ; pathology ; ROC Curve ; Viscosity

In view of the problem that there is no standard diagnosis for early stage keratoconus disease,at the same time to assist the special examiner and ophthalmologist to make the early diagnosis effectively,the advantages and disadvantages of each testing instrument were analyzed.In order to construct an assistant system for early diagnosis of keratoconus,a deep learning technique was applied in corneal OCT examination.The system used improved VGG-16 to realize the recognition accuracy of about 68% keratoconus keratopathy,and the clinical results showed that the system can help doctors to give diagnosis confidence to a certain extent.At the same time,the physician's re-marking of OCT can help train the system for more accurate judgment.
Corneal Topography ; Deep Learning ; Early Diagnosis ; Humans ; Keratoconus ; diagnostic imaging ; Tomography, Optical Coherence

PURPOSE: To assess the clinical efficacy of sequential intrastromal corneal ring segment (ICRS) implantation and corneal crosslinking (CXL) in corneal ectasia.METHODS: To assess the clinical efficacy of sequential intrastromal corneal ring segment (ICRS) implantation and corneal crosslinking (CXL) in corneal ectasia.RESULTS: Greater improvement in uncorrected visual acuity was observed in the ICRS + CXL group than in the ICRS or CXL alone groups at both 6 (p = 0.008) and 12 months (p = 0.028). Refractive errors of sphere and spherical equivalent were significantly reduced in both the ICRS (p = 0.002 at 6 months, p = 0.004 at 12 months) and ICRS + CXL groups (p < 0.001 at both 6 and 12 months). Keratometric values including the maximum, minimum, and average were significantly reduced in all 3 groups at postoperative 6 and 12 months; however, the greatest reductions were observed in the ICRS + CXL group (all p < 0.001).CONCLUSIONS: ICRS implantation followed by CXL within 1 month seems to be effective, and may be superior to ICRS or CXL alone in improving visual acuity and reducing refractive errors and keratometric values.
Collagen ; Cornea ; Dilatation, Pathologic ; Keratoconus ; Refractive Errors ; Treatment Outcome ; Visual Acuity

OBJECTIVE: To compare the corneal biomechanical properties among keratoconus, subclinical keratoconus and normal corneas by using CorVis ST, and to estimate the effect of these biomechanical indices in discriminating keratoconus and subclinical keratoconus from normal. METHODS: A total of 76 eyes of 67 subjects were enrolled and divided into three groups. Keratoconus group included 24 eyes from 17 patients, subclinical keratoconus group included 12 eyes from 12 patients and normal group included 40 normal eyes from 40 subjects．All the eyes were assessed with CorVis ST and ten biomechanical parameters, intraocular pressure (IOP) and central corneal thickness (CCT) were obtained from this machine. The discrimination of biomechanical characteristic of the three groups based on the all indices was reflected by discriminant analysis and the Fisher discriminant function was established. RESULTS: The values of corneal biomechanics of keratoconus, subclinical keratoconus, normal eyes were increased in sequence, except for three indices: the second applamation time (A2T), time taken to reach highest concavity (HCT) and maximum corneal velocity during the first applanation (Vin). Three sets of data were among a statistically significant difference (P<0.05). There were statistically significant differences (P<0.05) between any two groups by comparing with such two indices: radius value of central concave curvature at highest concavity (HCR) and CCT. The grades of the three groups were obvious, evaluated by the discriminant function. The accuracy of reevaluation was 85% by validation method. The biggest contribution of indices in discriminant function was given by such four indices in sequence: CCT, HCR, maximum deformation amplitude of highest concavity (HCDA) and maximum corneal velocity during the second applanation (Vout). CONCLUSION The corneal biomechanical properties of keratoconus and subclinical keratoconus were decreased compared with normal eyes. The biomechanical parameters based on CorVis ST showed a good performance for discriminating among keratoconus, subclinical keratoconus and normal corneas.
Biomechanical Phenomena ; Cornea ; Discriminant Analysis ; Humans ; Keratoconus ; Tonometry, Ocular

Objective: To determine the effect of corneal collagen cross-linking on the corneal curvature of eyes with keratoconus measured using an Oculus Pentacam® at 2 years and annually thereafter. Methods: This was a descriptive, retrospective study involving patients with keratoconus who had undergone uncomplicated collagen cross-linking using the Dresden protocol from January 2012 to March 2016. Baseline measurements of best-corrected visual acuity (BCVA), maximum K value (Kmax), corneal astigmatism, anterior and posterior elevation map changes were recorded and compared with data taken at 2 and 3 years Results: This study included 32 patients (48 eyes) with a mean follow-up of 28.88 ± 6.23 months. Only 4 patients (6 eyes) had 3-year follow-up data with a mean follow-up of 42.83 ± 4.58 months. When all eyes were considered, significant changes were noted in Kmax, BCVA, and anterior and posterior elevation maps between baseline and 2-year follow-up. Specifically, there were significant decreases in Kmax (p<0.0001) and anterior elevation (p<0.05), and significant improvement in BCVA (p<0.01) while posterior elevation (p<0.0001) was found to have increased significantly at 2nd year follow-up compared to baseline. When only eyes with 3-year follow-up data was analyzed, only BCVA showed significant change (p<0.05). Corneal astigmatism remained stable during the study period. Conclusion Two to 3 years after collagen cross-linking for keratoconus, corneal curvature parameters and BCVA showed improved and stable outcomes when compared to baseline.
Keratoconus ; Astigmatism

PURPOSE: To compare the effect of posterior corneal astigmatism on the estimation of total corneal astigmatism using anterior corneal measurements (simulated keratometry [K]) between eyes with keratoconus and healthy eyes. METHODS: Thirty-three eyes of 33 patients with keratoconus of grade I or II and 33 eyes of 33 age- and sex-matched healthy control subjects were enrolled. Anterior, posterior, and total corneal cylinder powers and flat meridians measured by a single Scheimpflug camera were analyzed. The difference in corneal astigmatism between the simulated K and total cornea was evaluated. RESULTS: The mean anterior, posterior, and total corneal cylinder powers of the keratoconus group (4.37 ± 1.73, 0.95 ± 0.39, and 4.36 ± 1.74 cylinder diopters [CD], respectively) were significantly greater than those of the control group (1.10 ± 0.68, 0.39 ± 0.18, and 0.97 ± 0.63 CD, respectively). The cylinder power difference between the simulated K and total cornea was positively correlated with the posterior corneal cylinder power and negatively correlated with the absolute flat meridian difference between the simulated K and total cornea in both groups. The mean magnitude of the vector difference between the astigmatism of the simulated K and total cornea of the keratoconus group (0.67 ± 0.67 CD) was significantly larger than that of the control group (0.28 ± 0.12 CD). CONCLUSIONS: Eyes with keratoconus had greater estimation errors of total corneal astigmatism based on anterior corneal measurement than did healthy eyes. Posterior corneal surface measurement should be more emphasized to determine the total corneal astigmatism in eyes with keratoconus.
Astigmatism* ; Cornea ; Humans ; Keratoconus* ; Meridians

OBJECTIVE: To investigate the effects of corneal thickness distribution and apex position on postoperative refractive status after full-bed deep anterior lamellar keratoplasty (FBDALK). METHODS: This is a retrospective analysis of patients who were diagnosed with advanced keratoconus between 2011 and 2014 in our hospital. The base of the cone in all patients did not exceed the central cornea at a 6-mm range. The FBDALK was performed by a same surgeon. All patients had a complete corneal suture removal and the follow-up records were intact. Patients who had graft-bed misalignment or who were complicated with a cataract or glaucoma were excluded. Uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BSCVA), and Pentacam examination data were recorded at two years postoperatively. The recorded data included the superior-inferior (S-I) and nasal-temporal (N-T) corneal thickness differences in 2, 4, 6, and 8 mm diameter concentric circles with the corneal apex as the center (S-I_{2 mm}, S-I_{4 mm}, S-I_{6 mm}, S-I_{8 mm}, N-T_{2 mm}, N-T_{4 mm}, N-T_{6 mm}, and N-T_{8 mm}), the linear, X-axis, and Y-axis distance between the corneal pupillary center and the cornea apex, total corneal astigmatism at a zone of 3 mm diameter from the corneal apex (TA_{3 mm}), the astigmatic vector values J₀ and J₄₅, and the corneal total higher-order aberration for 3 and 6 mm pupil diameters (HOA_{3 mm} and HOA_{6 mm}). Statistical analysis was performed by SPSS 15.0. RESULTS: A total of 47 eyes of 46 patients met the criteria and were included in this study. The mean follow-up time was (28±7) months. The mean UCVA was 0.45±0.23 (logMAR) (MAR: minimum angle of resolution) and the mean BSCVA was 0.19±0.15 (logMAR), which were all significantly positively correlated with postoperative TA_{3 mm} and HOA_{3 mm}. The mean S-I corneal thickness differences were (44.62±37.74) μm, and the mean N-T was (38.57±32.29) μm. S-I_{2 mm} was significantly positively correlated with J₀ (r=0.31), J₄₅ (r=0.42), HOA_{3 mm} (r=0.37), and HOA_{6 mm} (r=0.48). S-I_{4 mm} and S-I_{8 mm} were significantly positively correlated with HOA_{3 mm} (r=0.30, r=0.40) and HOA_{6 mm} (r=0.46, r=0.35). The X-axis distance between corneal pupillary center and corneal apex was significantly positively correlated with J₄₅ (r=0.29). CONCLUSIONS In patients with advanced keratoconus after FBDALK, the unevenly distributed thickness at corneal pupillary area and the misalignment of corneal apex and pupillary center might cause significant regular and irregular astigmatism, which affected the postoperative visual quality.
Adolescent ; Adult ; Cornea/surgery* ; Corneal Transplantation/methods* ; Cryopreservation ; Female ; Follow-Up Studies ; Humans ; Keratoconus/diagnosis* ; Keratoplasty, Penetrating/methods* ; Male ; Retrospective Studies ; Visual Acuity ; Young Adult