Search

Hironobu Jimura,1 Yuuki Mishima,1 Chie Sotozono,2 Akihide Watanabe,2 Jun Asai,3 Chiho Ohbayashi,4 Nahoko Ogata1 1Department of Ophthalmology, Nara Medical University, Nara, Japan; 2Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Department of Dermatology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 4Department of Diagnostic Pathology, Nara Medical University, Nara, JapanCorrespondence: Nahoko OgataDepartment of Ophthalmology, Nara Medical University, Nara, JapanTel +81-744-29-8884 (ext.3432)Fax +81-744-23-8032Email ogata@naramed-u.ac.jpAbstract: Primary acquired melanosis (PAM) of the conjunctiva is a potentially serious melanocytic lesion that can lead to the development of a melanoma. A 60-year-old woman noticed pigmentation of the conjunctiva of her left eye for more than 10 years. She underwent excisional biopsy combined with cryotherapy and was diagnosed with PAM without atypia by intraoperative consultation. She was followed for 7 years, and no changes were observed. Fourteen years after the initial biopsy, she noted a growing conjunctival tumor, and a melanoma was suspected. She underwent orbital exenteration and skin grafting procedures. Histopathological examination of the specimen led to a diagnosis of conjunctival malignant melanoma. Re-examination of the initial biopsy specimen revealed that there was a proliferation of melanocytes that partially expanded over the basal layer of the conjunctiva which had been diagnosed as PAM with moderate atypia. We conclude that this case of conjunctival PAM had progressed to a conjunctival malignant melanoma after 14 years. Pathological evaluation of intraepithelial lesions has its limitations; thus, cases of PAM, even in the absence of obvious atypia, require careful follow-up.Keywords: primary acquired melanosis, conjunctival malignant melanoma, malignant melanoma, conjunctival melanoma, conjunctival tumor

Norihiko Yokoi,1 Aoi Komuro,1 Chie Sotozono,1 Shigeru Kinoshita2 1Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan Purpose: Surgical punctal occlusion is indispensable for the treatment of severe dry eye in cases where punctal-plug insertion is not applicable due to an enlarged or deformed punctum. However, permanent punctal occlusion is difficult in some cases. In our aim to establish a more reliable punctal occlusion, we have devised a new surgical approach for punctal occlusion.Patients and methods: This study involved 20 puncta of 12 eyes of 12 patients (1 male and 11 females; mean age: 65.2 years) with severe aqueous-tear-deficient dry eye. A new surgical procedure for punctal occlusion using fibrous tissue from under the lacrimal caruncle into the diathermy-induced deepithelialized canaliculus as supporting tissue for punctal closure was performed. In all patients, the assessment of eye symptoms, as well as the condition of punctal occlusion by slit-lamp biomicroscopy, tear volume (tear-meniscus radius [TMR] measurement by meniscometry), the condition of precorneal tear film (graded by interferometry [IG]), measurement of fluorescein breakup time (FBUT), and scoring of ocular surface staining (fluorescein score of area [FSA] and density [FSD], and lissamine green score [LGS]) were performed, and the preoperative and 6-month-postoperative values were compared.Results: In regard to the postoperative improvement of symptoms, 11 patients showed remarkable improvement, 1 patient showed improvement, and no reopening of the closed punctum was found in any patient. Test values were all significantly improved post surgery (all: P

Osamu Hieda, Norihiko Yokoi, Chie Sotozono Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan Purpose: To report a case of filamentary keratitis occurring in the cornea hidden under the eyelids by squint surgery.Methods: A 69-year-old female patient with a history of amblyopia was referred for intractable filamentary keratitis in the left eye. The strabismus angle was 35Δ hypertrophic, and ocular motility was within the normal range. Slit-lamp examination of her left eye revealed filamentary keratitis in more than one-third of the upper cornea behind the upper eyelid. Her right eye was diagnosed as supranuclear double elevator palsy. We performed strabismus surgery on her right eye, including inferior rectus muscle recession (5 mm) in combination with superior rectus muscle resection (5 mm) under local anesthesia. Following surgery, the left eye squint angle was improved. The filamentary keratitis of the left eye disappeared, and there was no recurrence over the following 5 years.Conclusion: The squint surgery of paralyzed right eye decreased the strabismus angle, subsequently resulting in the disappearance of the filamentary keratitis in the left eye via the resolution of the relative blepharoptosis. Although the squint operation performed was not for the purpose of improving binocular function, we want to conclude that it can treat the filamentary keratitis behind the eyelid. Keywords: filamentary keratitis, squint surgery, double elevator palsy, amblyopia

Yoko Ikeda,1,2,* Kazuhiko Mori,1,* Kaori Tada,3 Morio Ueno,1 Shigeru Kinoshita,4 Chie Sotozono1 1Department of Ophthalmology, Kyoto Prefectural University of Medicine, 2Oike-Ganka Ikeda Clinic, 3Department of Ophthalmology, Japanese Red Cross Society Kyoto Daini Hospital, 4Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan *These authors contributed equally to this work Purpose: To evaluate and compare the intraocular pressure (IOP) reduction efficacy and safety between the ophthalmic solutions 0.005% latanoprost (Lat) and 0.0015% tafluprost (Taf) in Japanese patients with normal-tension glaucoma (NTG).Methods: In this randomized nonmasked study, we prospectively enrolled 30 Japanese NTG patients who had used Lat monotherapy for more than 4 weeks, and randomly divided them into the following two groups: 1) Lat-to-Taf group (LT group) and 2) Taf-to-Lat group (TL group). At the beginning of the study, both groups were switched from initial Lat to Lat or Taf for 12 weeks, and then switched over to the other drug (crossover) for 12 additional weeks. At 0, 4, 12, 16, and 24 weeks, we evaluated each patient’s IOP, conjunctival injection, and corneal epitheliopathy score, and at 0, 12, and 24 weeks, we evaluated their eyelash changes and pigmentation of the eyelids and irises.Results: The mean IOP of the LT group (15 eyes) was 10.5, 10.6, and 11.1 mmHg, at 0, 12, and 24 weeks, respectively, whereas that of the TL group (15 eyes) was 11.7, 11.1, and 10.5 mmHg at 0, 12, and 24 weeks, respectively. No significant differences were found between the two groups and in the intragroup comparisons. Moreover, no significant differences were found between Lat and Taf in regard to the conjunctival injection score and corneal epitheliopathy score. Eyelash changes and eyelid and iris pigmentation were similar in both groups.Conclusion: The findings of this study show that Lat and Taf have equivalent efficacy and safety in Japanese patients with NTG. Keywords: latanoprost, tafluprost, normal-tension glaucoma, crossover

BackgroundLong-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking.ObjectivesWe conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae.MethodsParticipants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method.ResultsFifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index

The article reviews and comments on a research which evaluated the ophthalmic efficacy of high-dose corticosteroid therapy for treating acute stage of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). It is pointed out that the use of systemic corticosteroids in the management of SJS/TEN remains controversial. Also, it reminds about the contraindication of intravenous pulse therapy with methylprednisolone in patients with infection such as sepsis.

Purpose: To investigate whether genetic and clinical characteristics differ depending on generations using 326 patients (male/female, 259/67; mean age, 55.4 ± 12.5 years) with simple CSC., Methods: All patients were diagnosed with simple CSC, defined as a retinal pigment epithelium alteration area equal to or smaller than 2-disc areas based on multimodal imaging at the initial presentation. We cross-sectionally evaluated clinical characteristics at the initial visit and genotyped CFH rs800292 and rs1329428 for all patients using TaqMan technology., Results: As generations decreased, the proportion of males, subfoveal choroidal thickness, and prevalence of fibrin significantly increased ( p  < 0.001, p  < 0.001, and p  = 0.012, respectively), and the best-corrected visual acuity improved ( p  < 0.001); in contrast, the prevalence of pachydrusen significantly decreased ( p  < 0.001). The younger presentation was significantly associated with male and risk variants (T allele) of CFH rs1329428 ( p  = 9.1 × 10 -7 and p  = 0.042, respectively), and patients were estimated to present 2 years younger per one T allele of CFH rs1329428 ( p  = 0.042, β = -1.95, stepwise regression analysis)., Conclusion: Clinical and genetic characteristics differed significantly among patients with simple CSC, depending on their generation.

Purpose: To investigate the motility of the primary cilia of corneal endothelial cells (CECs), which exist like a hair on the cell surface, using our new in vitro method., Methods: A white glass rod was heated with a gas burner to produce a rod approximately 0.5 mm in diameter and 20 mm in length and then coated with collagen. A suspension of cultured human CECs (HCECs) was then added to the rod and cultured for 20 days. Cells on the rod's side were then observed using phase-contrast microscopy, and videos and images of the primary cilia were obtained. After fixing the cells cultured on the rod's surface, immunofluorescence staining was performed and fluorescence and phase contrast images were taken., Results: Hair-like structures were observed on the surface of live HCECs on the rod's surface. Video images revealed that the structures sometimes swayed owing to slight convection of the medium, yet had no motile function, and immunostaining with acetylated α-tubulin antibody confirmed that the structures were primary cilia., Conclusions: Our new method using white glass rods provided the ability to observe the movement of primary cilia in cultured living HCECs, and the findings clearly showed that the primary cilia of HCECs are passive rather than motile. This novel procedure can be applied widely to other cultured cells as a method to observe the movement of primary cilia from the lateral aspect of the cell., Translational Relevance: This method may help to clarify the role of primary cilia in the anterior chamber.

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: Dermatologic 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. Ophthalmologic 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 < .001) and specific year in the survey (P < .001)., Conclusions: The ophthalmologic prognosis of SJS/TEN has dramatically improved via early diagnosis, rapid assessment of acute ocular severity, and early treatment., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate the significance of regulatory T cells (Tregs) and programmed cell death 1 (PD-1) + cytotoxic T lymphocytes (CTLs) in the vitreous of patients with vitreoretinal lymphoma (VRL) and uveitis., Methods: This study involved 51 patients with VRL and uveitis, 15 males and 36 females (mean age: 72 years, range: 51-86 years), who underwent vitrectomy at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan, from December 2019 to February 2024. All patients underwent lymphocyte surface antigen analysis via flow cytometry, and the proportion of Tregs in CD4 + T lymphocytes and PD-1 + CTLs in CD8 + T lymphocytes was measured., Results: This study involved B cell VRL (B-VRL, n=16), sarcoidosis (n=8), human herpesvirus (HHV)-associated uveitis (n=7), human T cell lymphotropic virus type 1 associated uveitis (HAU, n=3) and unclassifiable uveitis (n=17) cases. The median proportions of Tregs were significantly lower in B-VRL (2.2%) compared with sarcoidosis (8.5%), HHV-associated uveitis (16.4%) and unclassifiable uveitis (10.1%) (p<0.05). Conversely, a significantly higher proportion of PD-1 + CTLs was found in B-VRL (95.6%) compared with sarcoidosis (61.1%), HHV-associated uveitis (67.1%) and unclassifiable (64.8%) (p<0.05). Receiver operating characteristic analysis of Tregs and PD-1 + CTLs proportions in B-VRL revealed high area under the curve values of 0.913 and 0.940, respectively., Conclusions: Our findings indicate that analysis of the ratio of Tregs and PD-1 + CTLs via flow cytometry is helpful in diagnosing B-VRL., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the visual prognosis of ocular surface squamous neoplasia (OSSN) after tumor resection and ocular surface reconstruction, and clarify factors that influence recurrence., Study Design: Retrospective cohort study., Methods: Medical records of all patients who underwent surgical treatment for OSSN at our hospital between January 1996 and December 2019 were reviewed. Tumor size/location, histological classification, surgical procedure, intraoperative mitomycin-C use, and postoperative topical 5-fluorouracil (5-FU) administration were examined, and pre and postoperative visual acuity (VA) were compared to elucidate factors that influence disease recurrence., Results: Tumor excision was performed in 70 eyes of 70 cases (43 men, 27 women; average age: 71.6 ± 12.6 years) with dysplasia (8 eyes), carcinoma in situ (26 eyes), and invasive squamous cell carcinoma (36 eyes). Tumors were found in the limbus (N = 59 eyes), palpebral conjunctiva (N = 8 eyes), and from the bulbar to palpebral conjunctiva (N = 3 eyes). Surgical procedures performed were limbal transplantation/keratoepithelioplasty (N = 29 eyes), cultivated oral mucosal epithelial transplantation (N = 3 eyes), and auto-conjunctival epithelium transplantation (N = 2 eyes). Ocular surface was reconstructed using amniotic membrane, donor cornea, or cultivated epithelial sheet. The mean follow-up was 38.6 ± 38.6 months (range, 2 months to 13.8 years). VA postoperatively improved in 25 (61.0%) cases. Recurrence occurred in 19 (27.1%) cases at from 2 to 50 months (median: 12.5 months) postoperative. Uni- and multivariate analyses revealed that presurgical tumor size and postoperative administration of 5-FU were significantly related to recurrence., Conclusion: Combined surgical excision and postoperative topical 5-FU administration effectively prevented OSSN recurrence, and ocular surface reconstruction contributed to improvement of VA., (© 2024. The Author(s).)

To evaluate the efficacy and safety of a cultured human corneal endothelial cell (cHCEC) product in eyes with bullous keratopathy (BK). Combined analysis of multicenter phase II and III clinical trials. This analysis involved 15 BK eyes in the phase II trial and 12 BK eyes in the phase III trial that underwent cHCEC transplant therapy. Safety was assessed in all the cases. Efficacy was assessed in 17 cases with exclusion of the low- and medium-dose groups in the phase II trial. The primary endpoint was a corneal endothelial cell density of 1000 cells/mm 2 or more at 24 weeks post-transplant, which was attained in 94.1% of the eyes (16 of 17), with a 95% CI of 71.3-99.9%. Additionally, 82.4% of the eyes (14 of 17) met the secondary endpoint of reduction in corneal thickness to less than 630 µm without corneal epithelial edema within the same time frame, with a 95% CI of 56.6-96.2%. The mean decrease in corneal thickness from baseline to 24 weeks post-transplant was -187.4 µm (95% CI, -240.2 µm to -134.5 µm). Furthermore, all the eyes exhibited improvement in best-corrected visual acuity from baseline to 24 weeks post-transplant (95% CI, 80.5-100.0%). By 24 weeks post-transplant, 88.9% of the patients (24 of 27) had experienced adverse events, which were mostly local, mild, and transient. The cHCEC product of this study reconstitutes the corneal endothelial layer with high cellular density and restores corneal thickness and improves visual acuity., (© 2024. Japanese Ophthalmological Society.)

Age-related macular degeneration (AMD) is associated with the dysfunction and degeneration of retinal pigment epithelium (RPE) cells. Here, we examined how the formation and expansions of cell clusters are regulated by the differentiation of the RPE　cells. In this study, ARPE-19 cells were cultivated in standard or differentiation media, i.e., without or with nicotinamide, to evaluate the spreading of cell clusters specified with differentiated cell phenotypes. Mitochondria membrane potential (MMP) and the distribution of the RPE cell clusters was also monitored with or without rotenone, a mitochondrial electron transport chain (ETC) complex I inhibitor. Cultured ARPE-19 cells generated scattered cell clusters composed mostly of smaller size cells expressing the differentiation markers mouse anti-cellular retinaldehyde-binding protein (CRALBP) and Bestrophin only in differentiation medium. After the increase of the number of clusters, the clusters appeared to paracellularly merge, resulting in expansion of the area occupied by the clusters. Of note, the cells within the clusters selectively had high MMP and were in accordance with the expression of RPE differentiation markers. Rotenone repressed the formation of the clusters and decreased intracellular MMP. The above results suggest that clustering of RPE cells with functional mitochondria plays a pivotal role in RPE cell differentiation process and the ETC complex I inhibition greatly influences the composition of RPE cells that are degenerated or differentiation disposed., (© 2024. The Author(s).)

Importance: Whether guttae in Fuchs endothelial corneal dystrophy (FECD) can be removed by polishing without Descemet stripping and whether postoperative maintenance of reduced guttae can be achieved through cultured corneal endothelial cell (CEC) transplant therapy are critical issues to be addressed., Objective: To investigate the decrease of guttae through polishing degenerated CECs and abnormal extracellular matrix (ECM) without Descemet stripping and to observe the behavior of guttae following cultured CEC transplant., Design, Setting, and Participants: This case series prospective observational study was conducted in a hospital outpatient clinic setting. Between December 2013 and January 2019, 22 eyes with corneal endothelial failure caused by FECD received cultured CEC transplant therapy at Kyoto Prefectural University Hospital. Of these, 15 eyes were consistently monitored at the same central corneal area during the preoperative phase, as well as in the early (within 1 year) and late (after 3 years) postoperative phases. The images from these phases were categorized into 3 groups: typical guttae, atypical guttae, and no guttae., Exposures: Cultured CEC transplant therapy., Main Outcomes: Proportion of guttae in the observable area was measured, comparing the early and late postoperative phases for each group., Results: The mean age of the patients at the time of surgery was 69 years (range, 49-79 years). All 15 eyes exhibited the presence of confluent guttae preoperatively (100%). Among these, 3 of 15 eyes belonged to male patients. The early postoperative phase of guttae morphologies was classified into 3 groups: 5 eyes with typical guttae, 7 with atypical guttae, and 3 with no guttae. The decrease in the number of these guttae was achieved by surgical procedures. The median percentage of guttae in the typical guttae, atypical guttae, and no guttae groups was 41.8%, 44.4%, and 16.2%, respectively, in the early phase, and 42.2%, 38.2%, and 18.8%, respectively, in the late phase., Conclusions and Relevance: The findings demonstrate that in some cases of FECD, guttae can be removed by scraping and polishing abnormal ECM and degenerated CECs, while preserving the Descemet membrane. Furthermore, cultured CEC transplant resulted in no increase in guttae for up to 3 years, providing insights into surgically eliminating guttae.

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., (© 2024. Japanese Ophthalmological Society.)

Purpose: This report aims to document a long-term follow-up of a rare case of Brown-McLean syndrome where high-density central corneal endothelial cells (CECs) were maintained, yet the peripheral area developed corneal edema., Observations: A 72-year-old Japanese male was referred to our hospital. He had a history of three instances of rhegmatogenous retinal detachment in the right eye, requiring three intraocular surgeries. While the circumferential corneal peripheral regions, predominantly in the nasal and temporal areas, exhibited corneal edema, the central region remained clear. The central corneal thickness was measured at 541 μm, and the thickness in the nasal and temporal regions exceeded 700 μm. CEC density at the center was determined to be 2499 cells/mm 2 using a non-contact specular microscope, but imaging of the nasal and temporal cornea was obscure due to corneal edema. Panoramic images of the corneal endothelial layer, captured via slit-scanning wide-field contact specular microscopy, showed a high-density and uniform distribution of cells across the clear corneal region, close to the border between edematous and non-edematous areas. Twelve years after the initial visit, the central cornea maintained its transparency and a CEC density of 2456 cells/mm 2 . Despite the entire peripheral corneal edema, there was no noted deterioration from twelve years prior. The annual reduction in central cornea CECs was a mere 0.09 %., Conclusions and Importance: This case implies the unintended formation of a biological barrier at the border or a possible lack of CEC affinity of centrifugal movement, among other unidentified factors. Such factors may hinder the migration of CECs from the central to the peripheral regions of the cornea, a discovery that is crucial for advancing our knowledge of corneal endothelial biology and exploring new treatment options., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Inc.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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/mm 2 and 55.5% ± 13.9% in the high-maturity group and 853 ± 430 cells/mm 2 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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 β-galactosidase (SA-β-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-β-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.