Improvement of corneal epithelial damage after switching from the concomitant use of brinzolamide and brimonidine to a brinzolamide/brimonidine fixed-dose combination.

PURPOSE: To assess the effectiveness of switching from the concomitant use of brinzolamide 1% (BZM) and brimonidine 0.1% (BMD) to a BZM/BMD fixed-dose combination (BBFC) for the reduction of corneal epithelial damage. STUDY DESIGN: Retrospective cohort study. METHODS: This study involved 52 eyes of 52 glaucoma patients (26 women, 26 men; mean age: 67.0 ± 14.0 years) followed for more than 3 months after being switched from concomitant BZM and BMD to BBFC. Superficial punctate keratitis (SPK) was assessed by fluorescein staining according to the National Eye Institute classification, with the cornea divided into 5 areas: center, superior, nasal, temporal, and inferior. SPK density was graded as 0 (no SPK), 1 (separate SPK), 2 (moderately dense SPK), and 3 (high SPK with overlapping lesions). SPK scores and intraocular pressure (IOP) at pre switching to BBFC (pre-BBFC) and at 3-months post switching to BBFC (post-BBFC) were then compared using the Wilcoxon signed-rank test. RESULTS: At pre-BBFC and post-BBFC, respectively, mean IOP was 12.4 ± 2.5 and 12.4 ± 2.7 mmHg, thus illustrating no significant difference in IOP between pre and post switch (p = 0.924), and the mean SPK score for center, superior, nasal, temporal, and inferior was 0.06 ± 0.24, 0.04 ± 0.19, 0.52 ± 0.67, 0.15 ± 0.36, and 0.92 ± 0.74, and 0.04 ± 0.19, 0.02 ± 0.14, 0.37 ± 0.56, 0.04 ± 0.19, and 0.75 ± 0.62, thus clearly showing a significant reduction in SPK scores for the nasal, temporal, and inferior areas at post-BBFC compared to those at pre-BBFC (p < 0.05). CONCLUSION: Our findings reveal that compared with the concomitant use of BZM and BMD, BBFC is effective in reducing corneal epithelial damage.

Alteration of Gene Expression in Pathological Keratinization of the Ocular Surface.

Purpose: To investigate the molecular mechanism of pathological keratinization in the chronic phase of ocular surface (OS) diseases. Methods: In this study, a comprehensive gene expression analysis was performed using oligonucleotide microarrays on OS epithelial cells obtained from three patients with pathological keratinization (Stevens-Johnson syndrome [n = 1 patient], ocular cicatricial pemphigoid [n = 1 patient], and anterior staphyloma [n = 1 patient]). The controls were three patients with conjunctivochalasis. The expression in some transcripts was confirmed using quantitative real-time PCR. Results: Compared to the controls, 3118 genes were significantly upregulated by a factor of 2 or more than one-half in the pathological keratinized epithelial cells (analysis of variance P < 0.05). Genes involved in keratinization, lipid metabolism, and oxidoreductase were upregulated, while genes involved in cellular response, as well as known transcription factors (TFs), were downregulated. Those genes were further analyzed with respect to TFs and retinoic acid (RA) through gene ontology analysis and known reports. The expression of TFs MYBL2, FOXM1, and SREBF2, was upregulated, and the TF ELF3 was significantly downregulated. The expression of AKR1B15, RDH12, and CRABP2 (i.e., genes related to RA, which is known to suppress keratinization) was increased more than twentyfold, whereas the expression of genes RARB and RARRES3 was decreased by 1/50. CRABP2, RARB, and RARRES3 expression changes were also confirmed by qRT-PCR. Conclusions: In pathological keratinized ocular surfaces, common transcript changes, including abnormalities in vitamin A metabolism, are involved in the mechanism of pathological keratinization.

Improvement of the Ocular Prognosis of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A National Survey in Japan.

PURPOSE: To investigate the incidence and prognostic factors of ocular sequelae in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) cases arising between 2016 and 2018 in Japan, and compare the findings with those presented in the previous 2005-2007 survey. DESIGN: Retrospective, national trend survey . METHODS: Dermatological case report forms (CRFs) (d-CRFs) were sent to 257 institutions that treated at least 1 SJS/TEN case, and 508 CRFs were collected from 160 institutions. Ophthalmological CRFs (o-CRFs) regarding patient demographic data, onset date, ocular findings (first appearance, day of worst severity, and final follow-up), topical treatment (betamethasone), outcome (survival or death), and ocular sequelae (visual disturbance, eye dryness) were sent to the ophthalmologists in those 160 institutions. The results of this survey were then compared with that of the previous 2005-2007 survey. RESULTS: A total of 240 cases (SJS/TEN: 132/108) were included. The incidence of ocular sequelae incidence was 14.0%, a significant decrease from the 39.2% in the previous survey (SJS/TEN: 87/48). In 197 (82.1%) of the cases, systemic treatment was initiated within 3 days after admission, an increase compared to the previous survey (ie, treatment initiated in 82 [60.7%] of 135 cases). Of the 85 cases with an Acute Ocular Severity Score of 2 and 3, 62 (72.9%) received corticosteroid pulse therapy and 73 (85.9%) received 0.1% betamethasone therapy; an increase compared to the 60.0% and 70.8%, respectively, in the previous survey. Ocular-sequelae-associated risk factors included Acute Ocular Severity Score (P < 0.001) and specific year in the survey (P < 0.001). CONCLUSIONS: The ophthalmologic prognosis of SJS/TEN has dramatically improved via early diagnosis, rapid assessment of acute ocular severity, and early treatment.

Genetic and Clinical Characteristics of Central Serous Chorioretinopathy With Steroid Use.

PURPOSE: To compare the genetic and clinical characteristics of central serous chorioretinopathy (CSC) in patients with and without steroid use. METHODS: A total of 407 consecutive patients with CSC were included. Demographic data and clinical factors, including subfoveal choroidal thickness, bilateral involvement, descending tracts, pachydrusen, fibrin, and dome-shaped pigment epithelial detachment, were obtained. Variants of complement factor H (CFH) I62V (rs800292) and rs1329428 were genotyped in all cases using TaqMan technology. RESULTS: Of the total patients, 48 (11.8%) were steroid users. The majority of males were non-steroid users (82.5%) than steroid users (58.3%) (p = 9.8 × 10-5). Demographic data and the prevalence of clinical factors were comparable between the two groups (all p-values > 0.10). Risk allele frequencies of CFH rs800292 and rs1329428 were also comparable between the two groups (p = 0.76, rs800292: steroid users = 52.1% vs. non-steroid users = 50.4%; p = 0.62, rs1329428: steroid users = 47.9% vs. non-steroid users = 45.3%). CONCLUSIONS: Except for the male/female ratio, there were no significant differences in the clinical presentation or genetic characteristics, including variants of the CFH gene, between the two groups.

Senescent characteristics of human corneal endothelial cells upon ultraviolet-A exposure.

PURPOSE: The objective of this study was to investigate the senescent phenotypes of human corneal endothelial cells (hCEnCs) upon treatment with ultraviolet (UV)-A. METHODS: We assessed cell morphology, senescence-associated ß-galactosidase (SA-ß-gal) activity, cell proliferation and expression of senescence markers (p16 and p21) in hCEnCs exposed to UV-A radiation, and senescent hCEnCs induced by ionizing radiation (IR) were used as positive controls. We performed RNA sequencing and proteomics analyses to compare gene and protein expression profiles between UV-A- and IR-induced senescent hCEnCs, and we also compared the results to non-senescent hCEnCs. RESULTS: Cells exposed to 5 J/cm2 of UV-A or to IR exhibited typical senescent phenotypes, including enlargement, increased SA-ß-gal activity, decreased cell proliferation and elevated expression of p16 and p21. RNA-Seq analysis revealed that 83.9% of the genes significantly upregulated and 82.6% of the genes significantly downregulated in UV-A-induced senescent hCEnCs overlapped with the genes regulated in IR-induced senescent hCEnCs. Proteomics also revealed that 93.8% of the proteins significantly upregulated in UV-A-induced senescent hCEnCs overlapped with those induced by IR. In proteomics analyses, senescent hCEnCs induced by UV-A exhibited elevated expression levels of several factors part of the senescence-associated secretory phenotype. CONCLUSIONS: In this study, where senescence was induced by UV-A, a more physiological stress for hCEnCs compared to IR, we determined that UV-A modulated the expression of many genes and proteins typically altered upon IR treatment, a more conventional method of senescence induction, even though UV-A also modulated specific pathways unrelated to IR.

A new surgical approach for the treatment of a refractory foveal microaneurysm: A case report.

Purpose: To report a case of a refractory foveal microaneurysm (MA) that was successfully treated by use of a new surgical procedure. Observations: This study involved a 79-year-old female with an active foveal MA associated with branch retinal vein occlusion in her left eye. Despite anti-vascular endothelial growth factor treatments, the MA remained active without closure, and best-corrected visual acuity (VA) gradually decreased from 20/20 to 20/200. After our new surgical procedure was explained in detail to the patient, written informed consent was obtained from the patient and the surgery was performed. Briefly, following pars plana vitrectomy, the internal limiting membrane in her left eye was peeled and the retina of the external wall of the MA was then gently incised. The exposed MA was then directly grabbed and pulled up onto the retina using 27-gauge microforceps, and photocoagulation was performed. At 3-months postoperative, closure of the MA and improvement in the retinal findings were observed, and best-corrected VA improved to 20/67. Conclusions and importance: We report a case of a refractory foveal MA that was successfully treated with a novel surgical technique that closed the MA, avoided thermal damage to the surrounding tissue, and resulted in improved postoperative VA.

The Features and Treatment Effects on Keratoepitheliopathy for Meibomitis-Related Keratoconjunctivitis.

Meibomitis-related keratoconjunctivitis (MRKC) is characterized by meibomitis with corneal epithelial abnormalities, and can be divided into two types: MRKC accompanied with phlyctenular keratitis, and MRKC accompanied with keratoepitheliopathy that is similar to superficial punctate keratopathy (SPK). The purpose of this retrospective study was to investigate the characteristic features of keratoepitheliopathy and treatment outcomes for MRKC. This study involved 27 eyes of 18 MRKC patients (3 males and 15 females). National Eye Institute (NEI) scores and visual acuity were compared at pre and post treatment. All subjects were treated with a small-dose administration of clarithromycin. Keratoepitheliopathy characteristic to MRKC, yet different in appearance from SPK, was noted in 24 of the 27 eyes. Fluorescein staining revealed granular epithelial lesions generally larger than SPK that coexisted with small dark spots. In 17 eyes, keratoepitheliopathy was located within the pupillary zone, and the visual acuity in 12 eyes was less than 1.0. Our findings showed significant improvement in the NEI score in MRKC (p < 0.0001) and in visual acuity (p = 0.0157) post treatment, and the characteristic features of keratoepitheliopathy in MRKC that are often associated with decreased visual acuity were elucidated. The treatment of clarithromycin was found to be effective for MRKC with keratoepitheliopathy.

Potential marker subset of blood-circulating cytokines on hematopoietic progenitor-to-Th1 pathway in COVID-19.

In this study, we analyzed a relatively large subset of proteins, including 109 kinds of blood-circulating cytokines, and precisely described a cytokine storm in the expression level and the range of fluctuations during hospitalization for COVID-19. Of the proteins analyzed in COVID-19, approximately 70% were detected with Bonferroni-corrected significant differences in comparison with disease severity, clinical outcome, long-term hospitalization, and disease progression and recovery. Specifically, IP-10, sTNF-R1, sTNF-R2, sCD30, sCD163, HGF, SCYB16, IL-16, MIG, SDF-1, and fractalkine were found to be major components of the COVID-19 cytokine storm. Moreover, the 11 cytokines (i.e., SDF-1, SCYB16, sCD30, IL-11, IL-18, IL-8, IFN-γ, TNF-α, sTNF-R2, M-CSF, and I-309) were associated with the infection, mortality, disease progression and recovery, and long-term hospitalization. Increased expression of these cytokines could be explained in sequential pathways from hematopoietic progenitor cell differentiation to Th1-derived hyperinflammation in COVID-19, which might also develop a novel strategy for COVID-19 therapy with recombinant interleukins and anti-chemokine drugs.

The existence of senescent cells in conjunctival epithelium from elderly individuals.

PURPOSE: The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16INK4a-expressing senescent cells in healthy human conjunctiva. STUDY DESIGN: Clinical and experimental. METHODS: Healthy conjunctival tissue samples were obtained from middle-aged and elderly subjects. RT-qPCR was performed to assess the expression of senescence markers CDKN2A (p16INK4a) and CDKN1A (p21CIP1/WAF1) and immunostaining was performed to examine the expression of the senescence marker p16INK4a, stem cell markers Ki67 and p63, tight-junction marker ZO-1. RESULTS: Our study involved 19 conjunctival tissue samples (10 elderly and 9 middle-aged), mean age [elderly: 75.8 ± 3.7 years (72-81), middle-aged: 52.7 ± 7 years (38-59)], sex (elderly: 3 men, 7 women; middle-aged: 3 men, 6 women). The expression of p16INK4a was significantly increased at the RNA level in the elderly compared to middle-aged (p < 0.05). Positivity rate of p16INK4a was significantly elevated in the elderly (15.0 ± 7.8%) compared to middle-aged (0.2 ± 0.6%) (p < 0.05). Positivity rate of Ki67and p63 was significantly reduced in the elderly (1.7 ± 1.7% and 16.5 ± 9.5%) compared to middle-aged (3.9 ± 1.8% and 24.7 ± 5.7%) (p < 0.05). ZO-1 expression was reduced in tissue samples showing p16INK4a-positivity but retained in tissue samples in which p16INK4a was undetectable. CONCLUSIONS: Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells.

Donor Corneal Endothelial Cell Maturity and Its Impact on Graft Survival in Glaucoma Patients Undergoing Corneal Transplantation.

PURPOSE: To examine corneal graft survival via corneal endothelial cell density (ECD) and corneal endothelial cell loss (ECL) at 5 years post-transplantation in the eyes of patients with and without a history of undergoing glaucoma surgery according to the maturity of the donor corneal endothelial cells. DESIGN: Prospective cohort study. METHODS: This prospective cohort study included 17 patients with glaucoma and 51 patients without glaucoma who underwent Descemet's stripping automated endothelial keratoplasty or penetrating keratoplasty at the Baptist Eye Institute, Kyoto, Japan, between October 2014 and October 2016. Human corneal endothelial cells were cultured from residual peripheral donor cornea tissue, and the maturity of the cells was evaluated by cell surface markers (ie, CD166+, CD44-/dull, CD24-, and CD105-) using fluorescence-activated cell sorting. Kaplan-Meier analysis or the chi-square test was used to assess the rate of successful corneal graft survival post-transplantation. RESULTS: At 36 months postoperatively, the mean ECD and ECL in the glaucoma-bleb eyes were 1197 ± 352 cells/mm2 and 55.5% ± 13.9% in the high-maturity group and 853 ± 430 cells/mm2 and 67.7% ± 18.1% in the low-maturity group, respectively. Kaplan-Meier analysis revealed that at 5 years postoperatively, the overall rate of survival was 45%, that is, 100% in the high-maturity group and 25% in the low-maturity group (P < .05). CONCLUSIONS: The findings in this prospective cohort study revealed that the use of donor corneal grafts containing mature-differentiated corneal endothelial cells could maintain the survival of the transplanted graft for a long-term period, even in patients with a history of undergoing glaucoma surgery.

Dematiaceous fungal keratitis caused by Cladophialophora boppii - A case report.

Purpose: To report a rare case of dematiaceous fungal keratitis caused by Cladophialophora boppii (C. boppii) in an immunocompromised patient. Observations: An 83-year-old male with chronic renal failure was referred to the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan due to persistent corneal epithelial defects (PEDs) in his left eye. Initial examination revealed decreased central corneal sensitivity and decreased tear secretion in that eye, both thought to be associated with herpetic keratitis. Permanent punctal-plug surgery combined with therapeutic soft contact lens wear was performed to treat the PED, which initially healed, yet recurred. Follow-up examination revealed a 1.0-mm-diameter black lesion consistent with the PED site, which subsequently increased in size, so treatment with miconazole solution eye drops, natamycin ophthalmic ointment, and systemic itraconazole was initially performed. Since the region of the lesion had progressed to corneal perforation, corneal transplantation surgery under general anesthesia was scheduled, yet the patient refused to undergo surgery. Mycological testing via DNA sequencing of the internal transcribed spacer of ribosomal DNA regions revealed that the isolate or pathogen was C. boppii. Mycotic keratitis caused by C. boppii was found to be resistant to antifungal drugs. Conclusion and importance: This is a rare case of fungal keratitis caused by C. boppii in an elderly immunocompromised patient.

Identification and Analysis of Primary Cilia in the Corneal Endothelial Cells of Patients with Bullous Keratopathy.

PURPOSE: To identify primary cilia in human corneal endothelial cells (CECs) obtained from patients with bullous keratopathy (BK). METHODS: This study involved CEC specimens obtained from 10 eyes of 10 consecutive patients (three males and seven females; mean age: 74.5 years, range: 68-90 years) with BK who underwent Descemet's stripping automated endothelial keratoplasty at Baptist Eye Institute, Kyoto, Japan between August 2019 and September 2020. Three corneal buttons obtained from 3 patients who underwent penetrating keratoplasty for keratoconus were used as 'non-BK' controls. All specimens were evaluated with immunofluorescence staining using an antibody against acetylated α-tubulin. RESULTS: Ciliary expression was observed in six of the 10 CEC specimens; i.e. in two specimens obtained from BK patients after glaucoma surgery (trabeculectomy), in two specimens obtained from patients with Fuchs endothelial corneal dystrophy, and in two specimens obtained from a patient with BK after laser iridotomy for primary angle closure. There was acetylated α-tubulin staining but no hair-like structures in two specimens, and ciliary expression was unknown in two specimens due to the absence of cells. The length of the primary cilia varied between all specimens. In contrast, no primary cilia were observed in the corneal buttons obtained from the three keratoconus patients. CONCLUSION: The findings in this study clearly demonstrate the expression of primary cilia in the CECs of patients afflicted with BK.

Characteristics of Pre-Lens Tear Film Behavior in Eyes Wearing Delefilcon A Silicone Hydrogel Water Gradient Contact Lenses.

The pre-lens tear film (PLTF) over (i) delefilcon A silicone hydrogel water gradient (WG; 33-80% from core to surface) contact lenses (CLs) (SHWG-CLs) and (ii) subjects' own non-WG soft CLs (SCLs) (SO-SCLs) was studied in 30 eyes of 30 subjects to assess the hypothesized PLTF stabilization over SHWG-CLs. In both eyes, delefilcon A SHWG-CLs (DAILIES TOTAL1®; Alcon, Fort Worth, TX, USA) or SO-SCLs were worn. After 15 min of wearing each lens, the tear meniscus radius (TMR, mm), lipid-layer interference grade (IG) and spread grade (SG), and non-invasive breakup time (NIBUT, seconds) were evaluated and compared between the SHWG-CLs and the SO-SCLs. The comparison between the SHWG-CL and SO-SCL groups (SHWG-CL and SO-SCL, mean ± SD) revealed that TMRs temporarily decreased and reached a plateau value after 15 min (0.21 ± 0.06; 0.21 ± 0.06) compared to the value prior to CL insertion (0.24 ± 0.08; 0.25 ± 0.08), with no significant difference between the two groups. The NIBUT, IG, and SG values after 15 min of wearing the CLs were (9.7 ± 3.7; 4.7 ± 4.2), (1.0 ± 0.2; 1.8 ± 1.0), and (1.1 ± 0.4; 1.9 ± 1.5), respectively, and all values were significantly better in the SHWG-CL group (p < 0.0001, p = 0.0039, and p < 0.0001, respectively). We found that compared to the SO-SCLs, the maintenance of the PLTF on the SHWG-CLs was supported by the thicker and more stable PLTF.

Immunohistochemistry in an Adult Case of Bitot's Spots Caused by Vitamin A Deficiency.

Bitot's spots (BS) are the buildup of superficially located keratin in the conjunctiva and are early indicators of vitamin A deficiency (VAD), primarily due to malnutrition and malabsorption, thus leading to xerophthalmia. BS are particularly prevalent in developing countries, and their presence necessitates prompt vitamin A supplementation to avert blindness, with the immunohistochemical characteristics of BS aiding in understanding the extent of epithelial abnormalities and the efficacy of vitamin A supplementation. We describe the case of a 34-year-old male with persistent BS despite extensive vitamin A supplementation and topical treatments who underwent surgical excision of the BS followed by amniotic membrane transplantation, thus resulting in symptom relief and epithelialization, with no recurrence observed during follow-up. Histopathologic and immunohistochemical evaluations revealed expression of keratinization-related proteins, along with an absence of mucin-5AC-positive cells, suggesting impaired differentiation into goblet cells due to VAD. This case highlights the potential age-related disparity in the efficacy of vitamin A supplementation, emphasizing the need for early detection and a multidisciplinary approach in the management of VAD, especially in young adults. The favorable outcome of surgical intervention highlights its viability in the management of persistent BS and encourages further investigation to optimize therapeutic strategies for VAD-related ocular manifestations.

Association between Corneal Higher-Order Aberrations Evaluated with a Videokeratographer and Corneal Surface Abnormalities in Dry Eye.

Analysis of higher-order aberrations (HOAs) is one reported method for evaluating dry eye disease (DED)-related loss of visual function. Tear film (TF) instability and corneal epithelial damage (CED) are both reportedly responsible for HOAs in DED, although, to the best of our knowledge, there are no reported methods that allow concurrent evaluation of their effects. In this study, we used a videokeratographer (VK) to continuously measure HOAs in DED after eye opening and investigated factors of ocular surface abnormalities that determine HOAs. This study involved 96 DED cases that underwent DED symptom assessment with a questionnaire and examination of tear volume, TF abnormalities (i.e., TF lipid-layer interference grades and spreading grades, and non-invasive breakup time and fluorescein breakup time), and CED, and their correlation with HOAs evaluated via VK. The results show that HOAs at 1 or 2 s after eye opening can reflect TF instability and CED within the central 4-millimeter-diameter area of the optical zone in DED eyes concurrently. This finding may be useful for the rapid and non-invasive detection and evaluation of degraded visual function in DED cases with a variety of clinical features.

Ocular cicatricial pemphigoid following Dipeptidyl Peptidase-4 inhibitor use: A case report.

Purpose: To report a rare Ocular Cicatricial Pemphigoid (OCP) case in a patient taking a Dipeptidyl Peptidase-4 Inhibitor (DPP-4 inhibitor), a medication used for the management of type 2 diabetes, for at least six years. Observations: A 64-year-old male presented with refractory bilateral conjunctival inflammation and ocular discharge that had persisted for two months, despite multiple prior therapies for presumed bacterial conjunctivitis. Upon initial examination, clinical findings strongly suggested OCP, and he had elevated levels of anti-BP180 antibodies. Despite receiving systemic treatments such as steroid pulse therapy and therapeutic plasma exchange after discontinuing DPP-4 inhibitors, his condition progressively worsened, with manifestations such as forniceal shortening in his left eye. Consequently, the patient required keratoepithelioplasty, amniotic membrane transplantation in his left eye, and bilateral eyelid entropion surgery. His condition initially worsened for a time after discontinuing the DPP-4 inhibitor, but it gradually improved over time, and ocular surface surgical intervention was not required in the right eye. Conclusions and Importance: The findings in this study demonstrate that severe refractory OCP may occur while taking the DPP-4 inhibitor, thus indicating that a detailed interview regarding medications is essential for patients with ocular pemphigoid, especially those with type 2 diabetes.

Strategic combination of cultivated oral mucosal epithelial transplantation and postoperative limbal-rigid contact lens-wear for end-stage ocular surface disease: a retrospective cohort study.

PURPOSE: To provide the long-term outcome of patients with end-stage severe ocular surface disease (OSD) consecutively treated with cultivated oral mucosal epithelial transplantation (COMET) followed by limbal-rigid contact lens (CL)-wear therapy. DESIGN: Retrospective cohort. METHODS: In 23 eyes of 18 patients with severe OSD who underwent COMET surgery between 2002 and 2019 and who were followed with limbal-rigid CL-wear therapy for at least 1 year postoperative, patient demographics, best-corrected visual acuity (BCVA, logMAR), Ocular Surface Grading Scores (OSGS), surgical indication and adverse events were reviewed. Primary and secondary outcomes were BCVA and OSGS changes at baseline and final examination, respectively. RESULTS: This study involved 16 patients with Stevens-Johnson syndrome and 2 patients with mucous membrane pemphigoid (mean age: 59±15 years). The indications for COMET were as follows: corneal reconstruction for vision improvement (10 eyes (43.5%)), corneal reconstruction for persistent epithelial defect (4 eyes (17.4%)) and conjunctival (fornix) reconstruction for symblepharon release (9 eyes (39.1%)). The mean duration of CL-wear postsurgery was 6.4±3.9 years (range: 1.4 to 13.3 years). The mean BCVA at baseline and at final follow-up was logMAR 1.9±0.5 and 1.3±0.7, respectively (p<0.05). Compared with those at baseline, the OSGSs for symblepharon and upper and lower fornix shortening showed significant improvement at each follow-up time point post treatment initiation. No serious intraoperative or postoperative adverse events were observed. CONCLUSION: In patients afflicted with severe OSD, COMET combined with limbal-rigid CL-wear therapy postsurgery was found effective for vision improvement and ocular surface stabilisation.

Gene expression signatures of human senescent corneal and conjunctival epithelial cells.

PURPOSE: This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells. METHODS: We examined cell morphology, senescence-associated ß-galactosidase (SA-ß-gal) activity, cell proliferation, and expression of senescence markers (p16 and p21). RNA sequencing analysis was conducted to compare gene expression profiles between senescent and non-senescent cells. Finally, the potential involvement of senescent cells in the pathogenesis of ocular surface diseases was investigated. RESULTS: X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA-ß-gal activity, decreased cell proliferation, and increased expression of senescence markers, p16 and p21. RNA-seq analysis revealed substantial differences in gene expression profiles between senescent corneal (SCo) and conjunctival epithelial cells (SCj). Moreover, SCj were detected in pathological conjunctival tissues associated with limbal stem cell deficiency (LSCD) due to Stevens-Johnson syndrome or chemical burns, potentially being involved in abnormal differentiation. CONCLUSION: This study highlights the cellular and molecular characteristics of senescent ocular surface cells, particularly in SCj that show abnormal keratin expression, and their potential roles in severe ocular surface diseases and pathology.

Severe ocular complications of SJS/TEN and associations among pre-onset, acute, and chronic factors: a report from the international ophthalmology collaborative group.

We formed an international research collaboration that included Japan, South Korea, Brazil, Thailand, Taiwan, the UK, and the US (682 patients from 13 hospitals between 2005 and 2020), to better evaluate the role of race, ethnicity, and other risk factors in the pathophysiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Ophthalmologists often see SJS/TEN patients with severe ocular complications (SOC; frequency 50% SJS/TEN patients) when the patients are referred to them in the chronic stage after the acute stage has passed. Global data were collected using a Clinical Report Form, capturing pre-onset factors, as well as acute and chronic ocular findings. Key conclusions of this retrospective observational cohort study were as follows: (1) Ingestion of cold medications [acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs)] was significantly and positively correlated with trichiasis, symblepharon, and/or conjunctivalization of the cornea in the chronic stage; (2) common cold symptoms prior to onset of SJS/TEN were significantly and positively correlated with acute conjunctivitis and ocular surface erosions in the acute stage and with trichiasis and symblepharon and/or conjunctivalization of the cornea in the chronic stage; (3) patients with SJS/TEN who presented with SOC tended to be female; (4) patients less than 30 years of age are more likely to develop SOC in the acute and chronic stages of SJS/TEN; (5) patients with acute severe conjunctivitis with ocular surface erosion and pseudomembrane formation in the acute stage are more likely to develop ocular sequelae in the chronic stage; and (6) onychopathy in the acute stage was positively correlated with ocular sequelae in the chronic stage. Our findings show that the ingestion of cold medications, common cold symptoms prior to the onset of SJS/TEN, and a young age might strongly contribute to developing the SOC of SJS/TEN.