Refractive Errors, Retinal Findings, and Genotype of Tuberous Sclerosis Complex: A Retrospective Cohort Study.

PURPOSE: To examine the refractive errors, retinal manifestations, and genotype in tuberous sclerosis complex (TSC) patients in a Korean population. MATERIALS AND METHODS: A total of 98 patients with TSC were enrolled in Severance Hospital for a retrospective cohort study. The number of retinal astrocytic hamartoma and retinal achromic patch within a patient, as well as the size, bilaterality, and morphological type were studied. In addition, the refractive status of patients and the comorbidity of intellectual disability and epilepsy were also examined. RESULTS: Retinal astrocytic hamartoma was found in 37 patients, and bilateral invasion was observed in 20 patients (54%). TSC1 mutation was associated with myopia (p=0.01), while TSC2 mutation was associated with emmetropia (p=0.01). Retinal astrocytic hamartoma was categorized into three morphological types and examined as follows: type I (87%), type II (35%), and type III (14%). Single invasion of retinal astrocytic hamartoma was identified in 32% of the patients, and multiple invasions in 68%. The TSC1/TSC2 detection rate was 91% (41/45). Among them, TSC1 variant was detected in 23 patients (54%), whereas TSC2 variant was detected in 18 patients (40%). The results showed that TSC2 mutations are correlated with a higher rate of retinal astrocytic hamartoma involvement (all p<0.05), and multiple and bilateral involvement of retinal hamartomas (all p<0.05). However, the size of retinal astrocytic hamartomas, comorbidity of epilepsy, or intellectual disability did not show correlation with the genetic variant. CONCLUSION: TSC1 variant patients were more myopic, while TSC2 variant patients showed association with more extensive involvement of retinal astrocytic hamartoma.

Presbyopia correction using the monocular bi-aspheric ablation profile in myopic eyes.

PURPOSE: To analyze the 6-month outcomes of the treatment combination of the monocular bi-aspheric ablation profile (PresbyMAX) and contralateral aspheric monofocal laser in situ keratomileusis (LASIK) ablation profile for correction of myopia and presbyopia. SETTING: Yonsei University College of Medicine and Eyereum Eye Clinic, Seoul, South Korea. DESIGN: Retrospective case series. METHODS: This was a retrospective case review of 92 patients (184 eyes) diagnosed with myopia who underwent uneventful simultaneous bi-aspheric ablation in the nondominant eye and aspheric monofocal regular LASIK in the dominant eye to correct myopia and presbyopia between January 2017 and August 2020. Monocular and binocular uncorrected distance visual acuity (UDVA) and near visual acuity (UNVA), and corrected distance visual acuity and near visual acuity were analyzed postoperatively. RESULTS: At 6 months postoperatively, the mean UDVAs (logMAR) in the dominant and nondominant eyes were 0.01 ± 0.02 and 0.26 ± 0.15, respectively. Furthermore, all treated dominant eyes achieved 20/20 or better monocular UDVA, and 84% achieved 20/16 or better monocular UDVA. In the nondominant treated eyes, 89% achieved 20/50 or better monocular UDVA, 78% achieved 20/40 or better, and 34% achieved 20/32 or better. The binocular cumulative UDVA at 6 months postoperatively was 20/20 or better in all patients. All patients achieved J2 or better in binocular cumulative UNVA, and 83% achieved J1. CONCLUSIONS: Presbyopia correction using the combination of PresbyMAX in the near eye and aspheric monofocal regular LASIK in the distant eye is a safe and effective treatment for presbyopia in patients with myopia.

Analysis of keratometric measurements in accordance with axial length in an aged population.

To investigate keratometric measurements according to axial length in an aged population. Patients requiring cataract surgery with keratometric measurements from four different ophthalmic devices (autorefractor/keratometer, Scheimpflug imaging, corneal topography/ray-tracing aberrometry, and partial coherence interferometry) between January 2016 and March 2021 were reviewed retrospectively. Cases for which four ophthalmic devices were deployed in the same order a day were included in this investigation. The corneal curvature of the flattest and steepest meridian, mean corneal curvature, corneal astigmatism, steepest axis location, and axial length were evaluated. In total, 250 eyes (137 patients) were included in the analysis. A negative correlation was found between mean corneal curvature and axial length, with correlation coefficients of 0.587, 0.592, 0.588, 0.591, 0.588, and 0.562 for autorefractor/keratometer, Scheimpflug imaging, corneal topography/ray-tracing aberrometry, partial coherence interferometry, total corneal refractive power of Scheimpflug imaging, and simulated keratometry of corneal topography/ray-tracing aberrometry measurements, respectively. No statistically significant differences were found for corneal astigmatism according to axial length. In axial length group of less than 26.0 mm, negative correlation was found between axial length and mean frontal corneal curvature while no correlation was found between axial length and corneal astigmatism. All four ophthalmic devices showed good inter-device reliability for mean corneal curvature but not corneal astigmatism.

Pembrolizumab-induced Stevens-Johnson Syndrome with Severe Ocular Complications.

PURPOSE: To report a unique case of Stevens-Johnson syndrome (SJS) with severe ocular complications induced by pembrolizumab, an immune checkpoint inhibitor. CASE PRESENTATION: A 64-year-old man with urothelial cancer presented with bilateral corneal epithelial defect and conjunctival pseudo-membrane formation with erythematous patches on the four extremities, abdomen, and back. He had urothelial cancer with multifocal lesions in the renal pelvis and left ureter, and para-aortic metastatic lymph nodes. Accordingly, pembrolizumab treatment was planned. Generalized skin eruption occurred 4 days after the first cycle of pembrolizumab treatment, and ocular symptoms occurred 2 weeks after the first cycle. The patient's symptoms improved after cessation of pembrolizumab treatment and administration of steroids systemically. CONCLUSIONS: Immune checkpoint inhibitors, including pembrolizumab, have been developed recently and are widely used in the treatment of various cancers. However, it should be noted that the drugs may cause adverse events such as SJS with severe ocular complications.

Prediction accuracy of conventional and total keratometry for intraocular lens power calculation in femtosecond laser-assisted cataract surgery.

This study evaluated the accuracy of total keratometry (TK) and standard keratometry (K) for intraocular lens (IOL) power calculation in eyes treated with femtosecond laser-assisted cataract surgery. The retrospective study included a retrospective analysis of data from 62 patients (91 eyes) who underwent uneventful femtosecond laser-assisted cataract surgery with Artis PL E (Cristalens Industrie, Lannion, France) IOL implantation by a single surgeon between May 2020 and December 2020 in Severance Hospital, Seoul, South Korea. The new IOLMaster 700 biometry device (Carl Zeiss Meditec, Jena, Germany) was used to calculate TK and K. The mean absolute error (MAE), median absolute error (MedAE), and the percentages of eyes within prediction errors of ± 0.25 D, ± 0.50 D, and ± 1.00 D were calculated for all IOL formulas (SRK/T, Hoffer-Q, Haigis, Holladay 1, Holladay 2, and Barrett Universal II). There was strong agreement between K and TK (intraclass correlation coefficient = 0.99), with a mean difference of 0.04 D. For all formulas, MAE tended to be lower for TK than for K, and relatively lower MAE and MedAE values were observed for SRK/T and Holladay 1. Furthermore, for all formulas, a greater proportion of eyes fell within ± 0.25 D of the predicted postoperative spherical equivalent range in the TK group than in the K group. However, differences in MAEs, MedAEs, and percentages of eyes within the above prediction errors were not statistically significant. In conclusion, TK and K exhibit comparable performance for refractive prediction in eyes undergoing femtosecond laser-assisted cataract surgery.

The identification of novel potential injury mechanisms and candidate biomarkers in renal allograft rejection by quantitative proteomics.

Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p < 0.05) with a significant finding that SUMO2 (small ubiquitin-related modifier 2) was identified as a "hub" protein for graft injury irrespective of causation. Sixty-nine urine proteins had differences in abundance (p < 0.01) in AR compared with stable graft, of which 12 proteins were up-regulated in AR with a mean fold increase of 2.8. Nine urine proteins were highly specific for AR because of their significant differences (p < 0.01; fold increase >1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of monitoring these urinary proteins for the specific and sensitive noninvasive diagnosis of acute renal allograft rejection.

Identification of secreted glycoproteins of human prostate and bladder stromal cells by comparative quantitative proteomics.

BACKGROUND: Functional development of the prostate is governed by stromal mesenchyme induction and epithelial response. Stromal/epithelial signaling can be mediated through direct cell-cell contact and diffusible factors and their cell surface receptors. These inducers are likely secreted or membrane-associated extracellular proteins. Given the importance of intercellular communication, it is possible that diseases like cancer could arise from a loss of this communication. One approach to gain a molecular understanding of stromal cells is to identify, as a first step, secreted stromal signaling factors. We proposed to do this by comparative analysis between bladder and prostate. METHODS: Secreted proteins were identified from cultured normal prostate and bladder stromal mesenchyme cells by glycopeptide-capture method followed by mass spectrometry. Differences in protein abundance between prostate and bladder were quantified from calculated peptide ion current area (PICA) followed by Western validation. Functional and pathway analyses of the proteins were carried out by Gene Ontology (GO) and Teranode software. RESULTS: This analysis produced a list of 116 prostate and 84 bladder secreted glycoproteins with ProteinProphet probability scores > or =0.9. Stromal proteins upregulated in the prostate include cathepsin L, follistatin-related protein, neuroendocrine convertase, tumor necrosis factor receptor, and others that are known to be involved in signal transduction, extracellular matrix interaction, differentiation and transport. CONCLUSIONS: We have identified a number of potential proteins for stromal signaling and bladder or prostate differentiation program. The prostate stromal/epithelial signaling may be accomplished through activation of the ECM-receptor interaction, complement and coagulation cascades, focal adhesion and cell adhesion pathways.

Comparison of a label-free quantitative proteomic method based on peptide ion current area to the isotope coded affinity tag method.

Recently, several research groups have published methods for the determination of proteomic expression profiling by mass spectrometry without the use of exogenously added stable isotopes or stable isotope dilution theory. These so-called label-free, methods have the advantage of allowing data on each sample to be acquired independently from all other samples to which they can later be compared in silico for the purpose of measuring changes in protein expression between various biological states. We developed label free software based on direct measurement of peptide ion current area (PICA) and compared it to two other methods, a simpler label free method known as spectral counting and the isotope coded affinity tag (ICAT) method. Data analysis by these methods of a standard mixture containing proteins of known, but varying, concentrations showed that they performed similarly with a mean squared error of 0.09. Additionally, complex bacterial protein mixtures spiked with known concentrations of standard proteins were analyzed using the PICA label-free method. These results indicated that the PICA method detected all levels of standard spiked proteins at the 90% confidence level in this complex biological sample. This finding confirms that label-free methods, based on direct measurement of the area under a single ion current trace, performed as well as the standard ICAT method. Given the fact that the label-free methods provide ease in experimental design well beyond pair-wise comparison, label-free methods such as our PICA method are well suited for proteomic expression profiling of large numbers of samples as is needed in clinical analysis.