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Akira Kobayashi,1 Takahiko Hayashi,2 Ami Igarashi,2 Toshiki Shimizu,2 Hideaki Yokogawa,1 Kentaro Yuda,3 Björn Bachmann,4 Satoru Yamagami,2 Kazuhisa Sugiyama1 1Department of Ophthalmology, Kanazawa University Hospital, Ishikawa, Japan; 2Department of Ophthalmology and Department of Visual Sciences, Nihon University School of Medicine, Itabashi, Tokyo, Japan; 3Kikuna Yuda Eye Clinic, Yokohama, Japan; 4Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyCorrespondence: Akira Kobayashi, Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Takara-machi 13-1, Kanazawa, Ishikawa-ken, 920-8641, Japan, Tel +81-76-265-2403, Fax +81-76-222-9660, Email eyekoba@gmail.comBackground: Currently, the push-in technique through the corneal tunnel using a blunt-tip spatula is used to insert an artificial corneal endothelium (EndoArt) into the anterior chamber (AC). The device is useful for patients with bullous keratopathy; however, it may be difficult to manipulate the very thin implant through hazy cornea. Unlike DMEK graft, it cannot be stained and the F-mark is faint. So, visualizing and orienting the implant is a real challenge especially through a hazy cornea and inadequate AC visualization. Therefore, alternative EndoArt implantation techniques are needed in patients with advanced endothelial dysfunction to avoid complications.Purpose: To report an alternative technique for EndoArt implantation using a Busin glide.Technique: The EndoArt was loaded onto the Busin glide with the concave side of the EndoArt facing upward and was then pulled/pushed into the Busin glide opening. After the Descemet’s membrane and endothelium were detached and removed in a circular fashion in a patient with advanced corneal endothelial decompensation, the Busin glide was inserted into the corneal incision, and the EndoArt was slowly pulled into the AC using retractor forceps. Finally, the air was injected into the AC.Conclusion: The Busin glide-assisted pull-through technique smoothly and securely inserted the EndoArt into the AC without upside-down attachment. This alternative technique can be useful for patients with a history of repeat intraocular surgeries or trauma with severe corneal edema to avoid potential complications such as epithelial implantation cysts or downgrowth.Keywords: endothelial keratoplasty, artificial corneal endothelium, EndoArt, bullous keratopathy, Descemet’s membrane endothelial keratoplasty

Kazuya Mori,&ast; Yunyan Ye,&ast; Hideaki Yokogawa, Tsubasa Nishino, Akira Kobayashi, Natsuko Mori, Yuko Takemoto, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan&ast;These authors contributed equally to this workCorrespondence: Hideaki Yokogawa, Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Takara-machi 13-1, Kanazawa, Ishikawa-ken, 920-8641, Japan, Tel +81-76-265-2403, Fax +81-76-222-9660, Email hyoko@med.kanazawa-u.ac.jpPurpose: The purpose of this study was to highlight the manifestations of glaucoma associated with cytomegalovirus (CMV) corneal endotheliitis.Methods: We reviewed the 34 patients that met the diagnostic criteria for CMV endotheliitis in our hospital, with special attention to the glaucoma status, including onset of glaucoma, glaucoma in the fellow eye, visual field defects, intraocular pressure, and final outcomes.Results: Thirty-four eyes of 34 patients (mean age, 69.1 ± 13.1 years; 31 males [91.2%]) with CMV corneal endotheliitis were enrolled. Thirty-two eyes (94.1%) had a history of a glaucoma diagnosis, which had been treated for 10.0 ± 10.1 years. Glaucoma in the fellow eye was noted in 16 cases (47.1%) and a history of Posner-Schlossman syndrome was noted in 13 cases (38.2%). Visual fields measured using a Humphrey field analyzer were normal-to-early stage (MD>-6dB) in 16 eyes (47.1%) and middle-to-late stage (MD≤-6dB) in 18 eyes (52.9%). The intraocular pressure decreased from 22.4 ± 10.6 mmHg at the initial visit to 14.9 ± 7.9 mmHg after medical treatment, including 0.5% topical ganciclovir (GCV) with and without a systemic anti-CMV agent, corticosteroid eye drops, and an anti-glaucoma agent (p< 0.01). During the follow-up period of 4.8 ± 3.0 years (range, 0.2– 10 years), 16 eyes (47.1%) required glaucoma surgery, including filtering surgery (7 eyes) and trabeculotomy only (9 eyes).Conclusion: Our case series showed that most of the patients with CMV corneal endotheliitis had glaucoma. Although medical therapy, including 0.5% topical GCV, had efficacy in lowering the intraocular pressure, one-half of the cases required glaucoma surgery. Therefore, ophthalmologists should strive to make an earlier diagnosis of CMV corneal endotheliitis by utilizing PCR testing of aqueous humor samples to prevent sight-threatening glaucomatous damage.Keywords: cytomegalovirus, corneal endotheliitis, secondary glaucoma, antiviral treatment

Tsubasa Nishino, Akira Kobayashi, Natsuko Mori, Hideaki Yokogawa, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanCorrespondence: Akira KobayashiDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-Machi, Kanazawa-shi, Ishikawa-ken 920-8641, JapanTel +81-76-265-2403Fax +81-76-222-9660Email eyekoba@gmail.comPurpose: To investigate in vivo corneal changes of genetically confirmed Reis–Bücklers corneal dystrophy (RBCD) and Thiel–Behnke corneal dystrophy (TBCD) using anterior segment optical coherence tomography (AS-OCT).Design: A single-center, prospective, comparative case series.Methods: Seven patients from 3 pedigrees (3 males, 4 females) with RBCD [Arg124Leu (R124L) heterozygous missense mutation of human transforming growth factor beta-induced (TGFBI) gene] and 4 patients from 3 pedigrees (3 males, 1 female) with TBCD [Arg555Gln (R555Q) heterozygous missense mutation of TGFBI gene] were examined. Six patients with RBCD and three patients with TBCD exhibited recurrence after corneal surgery including penetrating keratoplasty, phototherapeutic keratectomy, and electrolysis. All patients were examined by slit-lamp biomicroscopy followed by AS-OCT. Selected AS-OCT images of the cornea were evaluated qualitatively for changes in shape and degree of light reflection of corneal deposits.Results: Slit-lamp biomicroscopy showed characteristic irregular gray opacities in Bowman’s layer in each dystrophy: a geographic pattern in RBCD and a honeycomb pattern in TBCD. In each dystrophy, distinct characteristic deposits were observed by AS-OCT as a banding lesion in Bowman’s layer and its adjacent epithelium/stroma. In RBCD, the banding lesion was highly reflective and sharply margined at the stroma. In contrast, deposits in TBCD in the same layer showed a saw-tooth pattern toward the epithelium and poorly margined at the stroma.Conclusion: AS-OCT is able to clearly identify characteristic in vivo corneal microstructural changes associated with RBCD and TBCD. As a result, in vivo differentiation of RBCD and TBCD can be achieved.Keywords: Reis–Bücklers corneal dystrophy, Thiel–Behnke corneal dystrophy, anterior segment optical coherence tomography, genetic mutational analysis, human transforming growth factor beta-induced gene, TGFBI

Hideaki Yokogawa, Akira Kobayashi, Natsuko Mori, Tsubasa Nishino, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanCorrespondence: Hideaki YokogawaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa-shi, Ishikawa-ken 920-8641, JapanTel +81-76-265-2403Fax +81-76-222-9660Email hyoko@med.kanazawa-u.ac.jpPurpose: To describe the visibility of the retina through an air-filled anterior chamber during simultaneous pars plana vitrectomy (PPV) and Descemet’s stripping automated endothelial keratoplasty (DSAEK), and to discuss the technical challenges of a fluid-air exchange under such conditions.Methods: Six eyes from 6 patients with coexisting bullous keratopathy and posterior segment problems such as vitreous opacity, retained silicon oil, intraocular lens subluxation, or aphakia underwent simultaneous PPV and DSAEK. In all cases, after completion of 25-gauge PPV with/without flanged intrascleral intraocular lens fixation, DSAEK donor tissue was inserted into the anterior chamber. Air was then injected into the anterior chamber to attach the donor graft to the back surface of the host cornea. At this point, the visibility of the retina was evaluated using endoillumination and a wide-angle viewing system.Results: In all cases, visibility of the retina through an air-filled anterior chamber, with the DSAEK donor attached, was sufficient to perform a fluid-air exchange.Conclusion: Our clinical observations of such rare but clinically important conditions indicate that simultaneous PPV and DSAEK is possible with fair visualization of the posterior segment including the retina.Keywords: Descemet’s stripping automated endothelial keratoplasty, pars plana vitrectomy

Tsubasa Nishino, Akira Kobayashi, Hideaki Yokogawa, Natsuko Mori, Kazuhisa SugiyamaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanPurpose: To present the changing indications and surgical techniques for keratoplasty during a 16-year period (2003–2018) at a tertiary referral hospital in Japan.Methods: Consecutive keratoplasty cases at Kanazawa University Hospital from January 2003 to December 2018 were retrospectively reviewed. Keratoplasty procedures included penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), anterior lamellar keratoplasty (ALK), Descemet’s stripping automated endothelial keratoplasty (DSAEK), and Descemet’s membrane endothelial keratoplasty (DMEK). Annual numbers and types of keratoplasty as well as underlying diseases for PK and total keratoplasty procedures were recorded, and annual trends were statistically analyzed using Cochran–Armitage test for trend.Results: A total of 801 keratoplasty procedures (PK, 319 cases; DALK, 57 cases; ALK, 9 cases; DSAEK, 371 cases; and DMEK 45 cases; mean age, 66.9±16.3 years) were performed for 595 patients (302 males [329 eyes, 419 cases], 293 females [345 eyes, 382 cases]) during the 16-year period. The proportion of PK procedures decreased significantly in the beginning and showed a slightly increasing trend after a plateau around 2015. DSAEK was increasing after 2006 and reached a plateau around 2012. Among 10 underlying diseases for total keratoplasty, corneal opacity and dermoid were decreasing linearly. Failed PK and failed DSAEK were increasing linearly in the beginning and reached a plateau followed by a decreasing trend. In terms of the underlying disease for PK, bullous keratopathy was decreasing in the beginning and reached a plateau around 2015. A total of 19 PK procedures were performed on cases with recalcitrant bullous kerstopathy (BK) after 2010.Conclusion: The distribution of keratoplasty procedures and underlying diseases changed significantly over 16 years at a tertiary referral hospital in Japan. PK procedure was significantly decreased and DSAEK procedure was significantly increased. PK for BK decreased significantly; however, PK remains a viable option for other recalcitrant corneal diseases.Keywords: Descemet’s stripping automated endothelial keratoplasty, Descemet’s membrane endothelial keratoplasty, penetrating keratoplasty

Natsuko Mori,1,2 Hideaki Yokogawa,1 Akira Kobayashi,1 Tsubasa Nishino,1,3 Kazuhisa Sugiyama11Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; 2Department of Ophthalmology, Saiseikai Kanazawa Hospital, Kanazawa, Japan; 3Department of Ophthalmology, Toyama Prefectural Central Hospital, Toyama, JapanPurpose: This study aimed to elucidate the frequency of surgery-induced iris abnormalities after Descemet membrane endothelial keratoplasty (DMEK) and their impact on postoperative clinical outcomes.Methods: In this retrospective study, medical records of 32 eyes from 28 consecutive patients (mean age, 65.7±13.4 years; 14 men, 18 women) who underwent DMEK (or triple DMEK) were reviewed. In all patients, inferior peripheral iridectomy was created leaving full intracameral air tamponade at the end of surgery. Sulfur hexafluoride gas was not used in any cases. Surgery-induced iris abnormalities such as pupillary shape changes and iris depigmentation were evaluated by 3 masked observers. Pre-existing abnormalities were excluded. Eyes were divided into two groups based on the presence of surgery-induced iris changes: Group A (with iris abnormalities) and Group B (without). Impacts on postoperative clinical outcomes such as vision and endothelial cell density were analyzed.Results: Surgery-induced iris abnormalities were seen in 15 eyes (Group A, 9 with pupillary shape change and 6 with iris depigmentation; 46.9%), and 17 eyes showed no abnormalities (Group B, 53.1%). No significant differences were detected between groups in age, sex, indication, simultaneous cataract surgery, pre- and 6-month postoperative vision, donor age, donor endothelial cell density, and 6- and 12-month postoperative endothelial cell density.Conclusions: Surgery-induced iris abnormalities were noted in almost half of the eyes after DMEK (46.9%) in this study. However, there was no association between visual outcomes or postoperative endothelial cell density and the iris changes.Keywords: surgery-induced iris abnormalities, DMEK

Tsubasa Nishino, Akira Kobayashi, Hideaki Yokogawa, Natsuko Mori, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: To report a 10-year review of endothelial keratoplasty (EK) procedures, Descemet’s stripping automated endothelial keratoplasty (DSAEK) and Descemet’s membrane endothelial keratoplasty (DMEK), and underlying diseases at a tertiary referral hospital in Japan. Study design: A single-center, retrospective case series. Methods: We retrospectively reviewed all medical records of bullous keratopathy (BK) surgically treated by EK (DSAEK/DMEK) at Kanazawa University Hospital from January 2007 to December 2016. Changes or modifications to the annual number of EK procedures and underlying diseases were analyzed. Results: During this period, 320 EK procedures (DSAEK: 288 cases, DMEK: 32 cases) were performed on 250 patients. Total annual EKs gradually increased from 19 to 45 cases between 2007 and 2016. The annual number of DSAEKs was stable, although the proportion of DSAEKs to other procedures decreased significantly as re-DSAEKs and DMEKs increased. BK after argon laser iridotomy (ALI) was the leading cause in 2007, followed by Fuchs’ endothelial dystrophy (FED) and failed penetrating keratoplasty. In 2016, BK after trabeculectomy (TLE) was most prevalent, followed by failed DSAEK, failed penetrating keratoplasty, and pseudophakic BK. The decreased ALI and FED, and increased BK after TLE and failed DSAEK were statistically significant. Conclusion: The distribution of EK procedures (DSAEK/DMEK) and underlying diseases changed over 10 years at a tertiary referral hospital in Japan. The proportion of re-DSAEK and DMEK increased among all EK procedures. Most significantly, among the underlying diseases, decreased ALI and FED and increased TLE and failed DSAEK were observed. Extended multicenter analysis may further elucidate the changes in EK procedures and the causes of BK in Japan. Keywords: argon laser iridotomy, trabeculectomy, reoperation, Fuchs’ endothelial dystrophy

Akira Kobayashi, Hideaki Yokogawa, Natsuko Mori, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan Objective: To report the in vivo laser confocal microscopy findings of corneas with keratoconus, with special attention to abnormality of Bowman’s layer and sub-Bowman’s fibrous structures (Kobayashi-structures [K-structures]).Methods: Sixteen keratoconic eyes in 8 consecutive patients with keratoconus (4 males, 4 females, mean age, 41.1 years) were included in this study. Slit-lamp biomicroscopic photos were taken with or without fluorescein staining. The existence of anterior corneal mosaic (ACM) after eyelid rubbing under fluorescein staining was documented. In vivo laser confocal microscopic examinations were performed for all patients in both the central cone and the peripheral cornea to examine the existence of K-structures.Results: According to the Amsler–Krumeich scale, the eyes were graded as follows: stage 1 (n=3), stage 2 (n=1), stage 3 (n=1), and stage 4 (n=11). ACM was observed in 7 eyes (61.1%) in the cone area and 16 eyes (100%) in the peripheral cornea among all keratoconic eyes enrolled in this study. In addition, K-structures were observed in the 7 eyes (61.1%) and 16 eyes (100%) in the peripheral cornea among all keratoconic eyes. The presence of the K-structures was completely matched (100%) with the presence of ACM in both the central cone and the peripheral cornea. In 11 eyes with stage 4 keratoconus, ACM and K-structure was absent in 9 eyes (81.8%) in the cone area. On the contrary, in 5 eyes with mild-to-moderate keratoconus (grade 1 to 3), ACM and K-structure was present in all eyes (100%) in the cone area. The absent ratio of ACM and K-structures in the cone area was significantly higher in stage 4 severe keratoconus compared to mild-to-moderate keratoconus (grade 1 to 3) (Fisher, P=0.005).Conclusion: The existence of ACM and K-structures in both the central cone and the peripheral cornea showed perfect accord in patients with keratoconus, indicating a strong association of ACM and K-structures in patients with keratoconus. With the progress of the keratoconus, it seemed that ACM and K-structure progressively disappeared, suggesting Bowman’s layer abnormalities due to keratoconus. Further study in larger groups of patients with keratoconus is required to fully understand the significance of ACM/K-structures in keratoconic eyes and their association with Bowman’s layer. Keywords: keratoconus, anterior corneal mosaic, K-structure, confocal microscopy

Hideaki Yokogawa, Akira Kobayashi, Natsuko Mori, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: To produce a two-dimensional reconstruction map of dendritic lesions in patients with herpes simplex keratitis (HSK) using in vivo confocal microscopy.Methods: Four eyes of four patients (mean 65.8 years) with HSK presenting with a dendritic lesion were enrolled. Slit-lamp biomicroscopy and in vivo laser confocal microscopy were performed. Acquired confocal images at the level of the epithelium were arranged and mapped into subconfluent montages. Changes in the shape and degree of light reflection of abnormal cells and deposits around dendritic lesions as well as other corneal layers were qualitatively evaluated.Results: Mapping of dendritic lesion was successful in all cases, and the subconfluent montages clearly showed the larger image of dendritic lesion. In all cases, the dendritic lesion consisted of hyperreflective irregular epithelial cells, and was surrounded by distorted and elongated epithelial cells. In three cases, hyperreflective deposits were noted at the midline of the lesion. The corneal stroma showed a hyperreflective honeycomb pattern. In two cases, inflammatory cells were observed at the level of endothelial cell layer.Conclusion: Mapping of dendritic lesions in patients with HSK was successful in all patients using in vivo confocal microscopy. Cellular level observation of dendritic lesion at a relatively larger magnification may help understand the in vivo morphological change of HSK. Further study in more patients with HSK and nonherpetic dendritic lesion is needed to utilize confocal microscopy images in differential diagnosis and follow-up of the epithelial lesions with dendrite. Keywords: herpetic epithelial keratitis, in vivo confocal microscopy, fluorescein slit-lamp photograph, hyperreflective irregular epithelial cells, dendritic lesion

Hideaki Yokogawa, Akira Kobayashi, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanPurpose: To report surgical therapies for corneal perforations in a tertiary referral hospital.Methods: Thirty-one eyes of 31 patients (aged 62.4±18.3 years) with surgically treated corneal perforations from January 2002 to July 2013 were included in this study. Demographic data such as cause of corneal perforation, surgical procedures, and visual outcomes were retrospectively analyzed.Results: The causes of corneal perforation (n=31) were divided into infectious (n=8, 26%) and noninfectious (n=23, 74%) categories. Infectious causes included fungal ulcer, herpetic stromal necrotizing keratitis, and bacterial ulcer. The causes of noninfectious keratopathy included corneal melting after removal of a metal foreign body, severe dry eye, lagophthalmos, canaliculitis, the oral anticancer drug S-1, keratoconus, rheumatoid arthritis, neurotrophic ulcer, atopic keratoconjunctivitis, and unknown causes. Initial surgical procedures included central large corneal graft (n=17), small corneal graft (n=7), and amniotic membrane transplantation (n=7). In two cases the perforation could not be sealed during the first surgical treatment and required subsequent procedures. All infectious keratitis required central large penetrating keratoplasty to obtain anatomical cure. In contrast, several surgical options were used for the treatment of noninfectious keratitis. After surgical treatment, anatomical cure was obtained in all cases. Mean postoperative best corrected visual acuity was better at 6 months (logMAR 1.3) than preoperatively (logMAR 1.8).Conclusion: Surgical therapies for corneal perforations in our hospital included central large lamellar/penetrating keratoplasty, small peripheral patch graft, and amniotic membrane transplantation. All treatments were effective. Corneal perforation due to the oral anticancer drug S-1 is newly reported. Keywords: corneal perforation, keratoplasty, amniotic membrane transplantation

Akira Kobayashi, Hideaki Yokogawa, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Abstract: Here we report a case of endothelial keratoplasty with infant donor tissue obtained after brain death. A 52-year-old man with endothelial dysfunction of unknown cause in the right eye underwent non-Descemet stripping automated endothelial keratoplasty (nDSAEK) with tissue from an infant donor (2 years). Intraoperative and postoperative complications were recorded. Best corrected visual acuity and donor central endothelial cell density were recorded preoperatively and postoperatively. Infant donor tissue preparation with a microkeratome set at 300 µm was successful; the donor tissue was extremely elastic and soft compared with adult tissue. The central endothelial cell density of the infant donor tissue was as high as 4,291 cells/mm2. No complications were observed during donor tissue (8.0 mm in diameter) insertion with the double-glide technique (Busin glide with intraocular lens sheet glide) or any of the other procedures. Best corrected visual acuity improved from 1.7 logMAR (logarithm of the minimum angle of resolution; 0.02 decimal visual acuity) preoperatively to 0.2 logMAR (0.6) after 6 months and 0.1 logMAR (0.8) after 1 year. The central endothelial cell density after 6 months was 4,098 cells/mm2 (representing a 4.5% cell loss from preoperative donor cell measurements), and the central endothelial cell density after 1 year was 4,032 cells/mm2 (6.0% decrease). Infant donor tissue may be preferably used for DSAEK/nDASEK, since it may not be suitable for penetrating keratoplasty or Descemet membrane endothelial keratoplasty. Keywords: brain death, non-Descemet stripping automated endothelial keratoplasty, infant donor, endothelial keratoplasty

Akira Kobayashi, Tomomi Higashide, Hideaki Yokogawa, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Objective: To report the in vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta (OI) with special attention to the abnormality of Bowman's layer and sub-Bowman's fibrous structures (K-structures). Patients and methods: Two patients (67-year-old male and his 26-year-old son) with OI type I were included in this study. Slit lamp biomicroscopic and in vivo laser confocal microscopic examinations were performed for both patients. Central corneal thickness and central endothelial cell density were also measured. Results: Although the corneas looked clear with normal endothelial density for both eyes in both patients, they were quite thin (386 µm oculus dexter (OD) (the right eye) and 384 µm oculus sinister (OS) (the left eye) in the father and 430 µm OD and 425 µm OS in the son). In both patients, slit lamp biomicroscopic and in vivo laser confocal microscopic examination showed similar results. Anterior corneal mosaics produced by rubbing the eyelid under fluorescein were completely absent in both eyes. In vivo laser confocal microscopy revealed an absent or atrophic Bowman's layer; a trace of a presumed Bowman's layer and/or basement membrane was barely visible with high intensity. Additionally, K-structures were completely absent in both eyes. Conclusion: The absence of K-structures and fluorescein anterior corneal mosaics strongly suggested an abnormality of Bowman's layer in these OI patients. Keywords: osteogenesis imperfecta, K-structure, confocal microscopy, Bowman's layer

Akira Kobayashi, Hideaki Yokogawa, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: To report the first case of Descemet membrane endothelial keratoplasty (DMEK) for bullous keratopathy (BK) secondary to argon laser iridotomy (ALI).Patient: A 71-year-old woman presented with decreased visual acuity in her right eye due to BK secondary to ALI that was performed 10 years prior.Results: Phacosurgery was performed first, followed by successful DMEK 4 months later. A DMEK shooter was used for donor insertion, which allowed for a stable anterior chamber during donor insertion, even when the anterior chamber was quite shallow. Also, removal of edematous epithelial cells and endoillumination probe-assisted DMEK was quite useful to visualize DMEK graft on the background of the dark brown iris seen in Asian eyes. The patient’s best corrected visual acuity rapidly increased from 20/200 to 25/20 after 1 month, with complete resolution of corneal edema.Conclusion: We reported the first successful DMEK case for BK secondary to ALI. The use of a DMEK shooter for donor insertion and endoillumination assistance to visualize the DMEK graft was a useful technique for BK secondary to ALI. Keywords: argon laser iridotomy, bullous keratopathy, endoillumination, DMEK

Hideaki Yokogawa,1 Akira Kobayashi,1 Natsuko Yamazaki,1 Yoshiki Ueta,2 Yoshihiro Hashimoto,2 Naoko Tachi,2 Kazuhisa Sugiyama11Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, 2Department of Ophthalmology, Shinseikai Toyama Hospital, Imizu-shi, JapanBackground: The purpose of this paper is to report our experience of Descemet’s stripping and non-Descemet’s stripping automated endothelial keratoplasty (DSAEK/nDSAEK) for microcorneas using 6.0 mm donor grafts.Methods: Three eyes of two patients (a 56-year-old woman and a 59-year-old woman) with microcornea and suffering from bullous keratopathy were treated with either DSAEK or nDSAEK. A small donor graft (6.0 mm) was inserted into the anterior chamber using a double glide (Busin glide and intraocular lens sheet glide) donor insertion technique. Both patients were followed for at least 12 months. Clinical outcomes, including intraoperative and postoperative complications, visual acuity, and endothelial cell density were evaluated.Results: In all three cases (100%), no intraoperative complications were noted. In one case with a flat keratometry value (32.13 D), a partial donor detachment was noted one day postoperatively, but it was reattached by rebubbling. In another case, rejection was noted 8 months postoperatively, but treatment with systemic corticosteroids was successful. A clear cornea remained in all three cases (100%), with best-corrected visual acuity greater than 20/100 (mean 20/50) at 12 months. Mean postoperative endothelial cell counts were 2,603 ± 18 cells/mm2 at 6 months (7.4% decrease from preoperative donor cell counts) and 1,799 ± 556 cells/mm2 at 12 months (36.5% decrease).Conclusion: We report for the first time the successful use of a small donor graft (6.0 mm) for DSAEK/nDSAEK in cases of microcornea. Additional studies using a large number of patients are required to evaluate fully the potential advantages and drawbacks of small diameter donor grafts for microcornea.Keywords: microcornea, Descemet’s stripping, non-Descemet’s stripping, automated endothelial keratoplasty, small donor grafts

Noriaki Murata, Hideaki Yokogawa, Akira Kobayashi, Natsuko Yamazaki, Kazuhisa SugiyamaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanBackground: In this paper, we report our experience of the clinical features of single and repeated globe rupture after penetrating keratoplasty.Methods: We undertook a retrospective analysis of single and repeated globe ruptures following keratoplasty in eight eyes from seven consecutive patients referred to Kanazawa University Hospital over a 10-year period from January 2002 to March 2012. We analyzed their ophthalmic and demographic data, including age at time of globe rupture, incidence, time interval between keratoplasty and globe rupture, cause of rupture, complicated ocular damage, and visual outcome after surgical repair.Results: Five patients (71.4%) experienced a single globe rupture and two patients (28.6%) experienced repeated globe ruptures. Patient age at the time of globe rupture was 75.4 ± 6.8 (range 67–83) years. Four of the patients were men and three were women. During the 10-year study period, the incidence of globe rupture following penetrating keratoplasty was 2.8%. The time interval between penetrating keratoplasty and globe rupture was 101 ± 92 months (range 7 months to 23 years). The most common cause of globe rupture in older patients was a fall (n = 5, 79.8 ± 3.7 years, all older than 67 years). Final best-corrected visual acuity was .20/200 in three eyes (37.5%). In all except one eye, globe rupture involved the graft-host junction; in the remaining eye, the rupture occurred after disruption of the extracapsular cataract extraction wound by blunt trauma.Conclusion: Preventative measures should be taken to avoid single and repeated ocular trauma following penetrating keratoplasty.Keywords: repeated globe ruptures, penetrating keratoplasty, postoperative complications, ocular trauma

Natsuko Yamazaki,1 Akira Kobayashi,1 Hideaki Yokogawa,1 Yasuhisa Ishibashi,2 Yosaburo Oikawa,3 Masaharu Tokoro,4 Kazuhisa Sugiyama11Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; 2Department of Ophthalmology, East Washinomiya Hospital, Kuki, Japan; 3Department of Medical Zoology, Kanazawa Medical University, Kahoku, Japan; 4Department of Parasitology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanPurpose: The purpose of the current study was to investigate ex vivo laser confocal microscopic findings of cultured Acanthamoeba trophozoites obtained from Acanthamoeba keratitis patients.Methods: Eight cultured samples of Acanthamoeba trophozoites from eight eyes of seven patients (mean age, 26.9 years; age range, 18–52 years) were used. Seven samples were from corneal scrapings of Acanthamoeba keratitis patients and one sample was from the solution in a soft contact lens case. Ex vivo laser confocal microscopy was performed to qualitatively evaluate the shape and degree of light reflection of the living Acanthamoeba trophozoites.Results: Ex vivo laser confocal microscopy demonstrated highly reflective, high-contrast Acanthamoeba trophozoites with no walls (mean size, 25.4 µm; range, 17.1–58.5 µm). The shapes of the trophozoites were highly pleomorphic, and some showed characteristic acanthopodia by laser confocal microscopy.Conclusion: Ex vivo laser confocal microscopy was effective in demonstrating cultured Acanthamoeba trophozoites of various shapes and sizes. The observations of the current study may be helpful when similar structures are identified under in vivo conditions.Keywords: Acanthamoeba, trophozoite, laser confocal microscopy

Hideaki Yokogawa,1 Akira Kobayashi,1 Natsuko Yamazaki,1 Yasuhisa Ishibashi,2 Yosaburo Oikawa,3 Masaharu Tokoro,4 Kazuhisa Sugiyama11Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, 2Department of Ophthalmology, East Washinomiya Hospital, Kuki, 3Department of Medical Zoology, Kanazawa Medical University, Kahoku, 4Department of Parasitology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanBackground: The purpose of this study was to report Acanthamoeba encystment in Bowman’s layer in Japanese cases of persistent Acanthamoeba keratitis (AK).Methods: Laser confocal microscopic images of the cornea were obtained in vivo from 18 consecutive eyes from 17 confirmed AK patients. Retrospectively, 14 cases treated over 4 months were categorized as a nonpersistent group and three cases that required prolonged therapy for more than 6 months were categorized as a persistent group. Clinical outcomes based on final best-corrected visual acuity were retrospectively analyzed, and selected confocal images were evaluated qualitatively for abnormal findings.Results: The final best-corrected visual acuity was significantly lower (P < 0.01) for patients in the persistent group compared with that in the nonpersistent group. At the initial visit, in vivo confocal microscopy demonstrated Acanthamoeba cysts exclusively in the epithelial layer in both the nonpersistent group (80%) and the persistent group (100%). At a subsequent follow-up visit, numerous Acanthamoeba cysts were observed in the epithelial cell layer and in Bowman’s layer in all patients with persistent AK, but Acanthamoeba cysts were undetectable in all cases with nonpersistent AK tested.Conclusion: Invasion of cysts into Bowman’s layer was characteristically observed in patients with persistence of AK. This finding suggests that invasion of Acanthamoeba cysts into Bowman’s layer may be a useful predictor for a persistent clinical course.Keywords: Acanthamoeba keratitis, Bowman’s layer, encystment

Akira Kobayashi, Hideaki Yokogawa, Kazuhisa SugiyamaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanBackground: The purpose of this study was to investigate pathological changes of the corneal cell layer in patients with map-dot-fingerprint (epithelial basement membrane) dystrophy by in vivo laser corneal confocal microscopy.Methods: Two patients were evaluated using a cornea-specific in vivo laser scanning confocal microscope (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT 2-RCM). The affected corneal areas of both patients were examined. Image analysis was performed to identify corneal epithelial and stromal deposits correlated with this dystrophy.Results: Variously shaped (linear, multilaminar, curvilinear, ring-shape, geographic) highly reflective materials were observed in the “map” area, mainly in the basal epithelial cell layer. In “fingerprint” lesions, multiple linear and curvilinear hyporeflective lines were observed. Additionally, in the affected corneas, infiltration of possible Langerhans cells and other inflammatory cells was observed as highly reflective Langerhans cell-like or dot images. Finally, needle-shaped materials were observed in one patient.Conclusion: HRT 2-RCM laser confocal microscopy is capable of identifying corneal microstructural changes related to map-dot-fingerprint corneal dystrophy in vivo. The technique may be useful in elucidating the pathogenesis and natural course of map-dot-fingerprint corneal dystrophy and other similar basement membrane abnormalities.Keywords: cornea, confocal microscopy, map-dot-fingerprint dystrophy, epithelial basement membrane dystrophy, Heidelberg Retina Tomograph 2 Rostock Cornea Module (HRT 2-RCM)

Akira Kobayashi, Hideaki Yokogawa, Kazuhisa SugiyamaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanAbstract: We describe a modified technique for loading donor corneal endothelial lamella onto a Busin glide® without causing wrinkles, as part of the procedure of Descemet-stripping automated endothelial keratoplasty. Briefly, after punching out a composite of the donor-endothelial lamella and a microkeratome-dissected cap, several drops of dispersive ophthalmic viscosurgical device are placed onto the endothelial surface. The Busin glide surface is then wetted with several drops of balanced salt solution. After the composite is transferred onto the Busin glide, hydrodissection of the potential space between the donor-endothelial lamella and the microkeratome-dissected cap is carefully performed to enable smooth detachment of these two lamellae. Whereas simply dragging the donor-endothelial lamella directly onto the glide can cause wrinkling or folding of the donor lamella, this technique enables smooth detachment of the composite without wrinkle or fold formation, and results in less endothelial cell damage.Keywords: DSAEK, Busin glide, endothelial keratoplasty

Although previous reports have suggested the efficacy of autologous bone marrow-impregnated collagen matrix experimentally and clinically, we occasionally encounter difficult wounds that fail to respond to the treatment. The current study retrospectively investigated the factors that affect clinical outcomes based on the hypothesis that periwound microcirculation may play a significant role. Fifty-three patients with chronic wounds received surgical debridement, followed by application of an autologous bone marrow-impregnated collagen matrix. The periwound transcutaneous oxygen tension (TcPO2) was evaluated ( n=39). The patients were retrospectively divided into successful and unsuccessful subgroups. Successful treatment was defined as wound closure by spontaneous healing or skin graft. The TcPO2 of the unsuccessful subgroup significantly decreased after debridement while that of the successful subgroup increased. Among various parameters, the TcPO2 at 4 days after debridement showed the strongest association with the success of the treatment. As reference data, we collected the information of the patients ( n=22) who received standard wound care, and they showed the same trend wherein the TcPO2 of the unsuccessful subgroup markedly decreased after debridement. Reactivity of the wound microcirculation to increased wound perfusion in response to the surgical debridement might be a key determinant for successful wound healing. [ABSTRACT FROM AUTHOR]

Purpose: Several techniques have been developed for graft unfolding approaches in Descemet membrane endothelial keratoplasty (DMEK). However, despite these techniques, graft deployment and configuration in eyes with deep anterior chambers remain challenging in some cases. Therefore, in this study, we described a modified technique for DMEK, known as the "double-bubble technique assisted by holding forceps.", Methods: This was a retrospective interventional case series. Patients who underwent DMEK between August 2022 and July 2023, including cases with a history of vitrectomy and scleral fixation of intraocular lens, were enrolled in this study. Two experienced surgeons performed DMEK. In brief, after graft insertion into the anterior chamber, the first bubble with a small volume of air was injected above the graft to open the tight roll, and the graft edge was held using a 25-gauge graft manipulator. The second bubble was injected underneath the graft for fixation, while the graft edge was grasped using forceps during gas injection. The graft was released from the forceps. Best spectacle corrected visual acuity, central corneal thickness, endothelial cell density, and incidence of postoperative complications were measured before and after DMEK., Results: Eleven eyes of 11 patients were included in this study (mean follow-up period, 4.5 ± 4.4 months). Best spectacle corrected visual acuity and central corneal thickness significantly improved postoperatively ( P < 0.001). Rebubbling was required in 2 eyes; no other postoperative complications or primary graft failure were observed., Conclusions: The present technique enables safe and feasible DMEK surgery in vitrectomized eyes with scleral fixated IOLs and in those with a deep anterior chamber., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is no consensus on the postoperative outcomes of tongue reconstruction. Therefore, the authors developed a novel risk model for predicting dysphagia after tongue reconstruction., Methods: This retrospective study was conducted by the Oral Pharyngeal Esophageal Operation and Reconstruction Analytical, or OPERA, group across 31 cancer centers and university hospitals in Japan. A total of 532 patients [390 (73.3%) men and 142 (26.7%) women; median age at surgery, 60 years (range, 15 to 88 years)] who were diagnosed with oral tongue squamous cell carcinoma and underwent tongue reconstruction following glossectomy between 2009 and 2013 were included. Independent risk factors were identified using univariate regression analysis and converted to a binary format for multivariate analysis. An integer value was assigned to each risk factor to calculate a total score capable of quantifying the risk of feeding tube dependence., Results: Overall, 54 patients (10.2%) required a feeding tube at the time of evaluation. Predictive factors for feeding tube dependence were advanced age, lower American Society of Anesthesiologists physical status, low body mass index, lower serum albumin, comorbid hypertension and diabetes, extended tongue defect, resection beyond the tongue, laryngeal suspension, postoperative radiation therapy, and no functional teeth. In multivariate logistic regression analysis, age greater than or equal to 58.5 years, postoperative radiation therapy, wider tongue defect, and body mass index less than 21.27 kg/m 2 earned 6, 4, 3, and 2 points, respectively, for a maximum total score of 15., Conclusion: The authors' risk model provides a mathematical tool for estimating the individual risk of postoperative feeding tube dependence before tongue reconstruction., Clinical Question/level of Evidence: Risk, III., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

Collagen disorders are chronic autoimmune diseases with a complex clinical course; however, the risk of breast cancer in patients with collagen disorders remains unclear. The present study aimed to investigate long-term outcomes in women with breast cancer and collagen disorders. A total of 25 patients with breast cancer and collagen disorders who were treated between January 2004 and December 2011 were included. The clinicopathological factors, treatment, recurrence-free survival (RFS) and overall survival (OS) were reviewed. The mean age was 56.4±12.6 years, and 14, eight and three patients had cancer of clinical stages I, II and III, respectively. Regarding comorbid collagen disorders, 11 patients had rheumatoid arthritis, four had systemic lupus erythematosus, four had polymyositis/dermatomyositis, two had mixed connective tissue disease, two had Sjogren's syndrome, one had scleroderma and one had adult-onset Still's disease. The expression statuses of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) were HR(+), HER2(+) and HR(-)HER2(-) in 20 (80.0%), four (16.0%) and four (16.0%) patients, respectively. A total of 22 (84.0%) patients received steroids or immunosuppressive drugs for collagen disorders. The collagen disorder group had a higher mean Ki-67 labeling index than the control group (41.1 vs. 20.8%; P=0.007). After median observation periods of 103 and 114 months, the RFS and OS rates were lower in the collagen group than in the control group (64.5 and 80.7% vs. 85.3 and 94.3%, respectively; P<0.01). Patients with breast cancer and collagen disorders had relatively high Ki-67 expression, and relatively low RFS and OS rates. Thorough follow-up is necessary for patients with breast cancer who also have collagen disorders and high Ki-67 values., Competing Interests: Akihiko Osaki reports grants and personal fees from Astra Zeneca, Eisai, Chugai, Nippon Kayaku, and Eli Lilly; grants from Kyowa Kirin, Daiichi Sankyo, Taiho, Novartis, MSD, Sawai, Covance, Maruho, Sanofi, Takeda, WJOG, and LabCorp; and personal fees from Shionogi and Pfizer, outside the submitted work. Toshiaki Saeki reports personal fees from Taiho, Eisai, Kyowa Kirin, Chugai, Ono, ASKA, Novartis, Astra Zeneca, Takeda, Eli Lilly, Pfizer, MiRteL, and Meiji Seika, outside the submitted work and grants from Nippon Kayaku. Hiroshi Ishiguro reports grants and personal fees from Eisai and Chugai; grants from Astra Zeneca, MSD, Eli Lilly, Daiichi Sankyo, Takeda, and Epcrsu; and personal fees from Pfizer, Kyowa Kirin, EP-Force, and Cancer and Chemotherapy Publishers, outside the submitted work. Takao Takahashi reports personal fees from Daiichi Sankyo, Tsumura, Hisamitsu, and Shionogi, outside the submitted work. Kazuo Matsuura, Yuki Ichinose, Akihiro Fujimoto, Ayaka Sakakibara, Asami Nukui, Hideki Yokogawa, Hiroko Shimada, and Aya Asano declare that they have no competing interests., (Copyright © 2023, Spandidos Publications.)

Vimentin is a stable mesenchymal immunohistochemical marker and is widely recognized as a major marker of mesenchymal tumors. The purpose of the present study was to investigate if the vimentin expression status might serve as a significant predictor of outcomes in patients with invasive breast carcinoma of no special type (IBC-NST) and to investigate, by comprehensive RNA sequencing analyses, the mechanisms involved in the heightened malignant potential of vimentin-positive IBC-NSTs. This study, conducted using the data of 855 patients with IBC-NST, clearly identified vimentin expression status as a very important independent biological parameter for accurately predicting the outcomes in patients with IBC-NST. RNA sequence analyses clearly demonstrated significant upregulation of coding RNAs known to be closely associated with cell proliferation or cellular senescence, and significant downregulation of coding RNAs known to be closely associated with transmembrane transport in vimentin-positive IBC-NSTs. We conclude that vimentin-positive IBC-NSTs show heightened malignant biological characteristics, possibly attributable to the upregulation of RNAs closely associated with proliferative activity and cellular senescence, and downregulation of RNAs closely associated with transmembrane transport in IBC-NSTs., (© 2023 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Prcis: Previous trabeculectomy and medical or surgical glaucoma treatment after Descemet's stripping automated endothelial keratoplasty (DSAEK) were significantly associated with endothelial cell loss and graft failure. The pupillary block was a significant risk factor for graft failure., Purpose: To evaluate the long-term risk factors associated with postoperative endothelial cell loss and graft failure after DSAEK in Japanese eyes, with special attention to glaucoma., Patients and Methods: This retrospective study involved 117 eyes of 110 consecutive patients with bullous keratopathy who had undergone DSAEK. The patients were classified into 4 groups: (1) no glaucoma group (n = 23 eyes), (2) primary angle closure disease group (n = 32 eyes), (3) glaucoma group that had previously undergone trabeculectomy (n = 44 eyes) (glaucoma with bleb), and (4) glaucoma group that had not previously undergone trabeculectomy (n = 18 eyes) (glaucoma without bleb)., Results: The cumulative 5-year graft survival rate was 82.1%. The cumulative 5-year graft survival rate among the 4 groups is as follows: no glaucoma (73%), primary angle closure disease (100%), glaucoma with bleb (39%), and glaucoma without bleb (80%). Multivariate analysis revealed that additional glaucoma medication and glaucoma surgery after DSAEK were independent risk factors for endothelial cell loss. Conversely, glaucoma with blebs and pupillary block were independent risk factors for graft failure after DSAEK., Conclusion: Previous trabeculectomy and medical or surgical glaucoma treatment after DSAEK were significantly associated with endothelial cell loss and graft failure. Pupillary block was a significant risk factor for graft failure., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We aimed to investigate the clinical characteristics and risk factors for graft rejection after keratoplasty in Japanese patients. We enrolled 730 cases (566 patients) of penetrating keratoplasty (PK, N = 198), Descemet's stripping automated endothelial keratoplasty (DSAEK, N = 277), non-Descemet's stripping automated endothelial keratoplasty (nDSAEK, N = 138), and Descemet membrane endothelial keratoplasty (DMEK, N = 117). The incidence, clinical characteristics, and possible risk factors for graft rejection were analyzed. Graft rejection occurred in 65 cases (56 patients, 8.9%). The incidence rate of rejection was highest with PK (3.45/100 person-years), followed by DSAEK (2.34), nDSAEK (1.55), and DMEK (0.24). Cox regression analysis revealed keratoplasty type, younger age, indications (such as failed keratoplasty and infection), and steroid eyedrop use as possible risk factors. In the multivariate model adjusting baseline characteristics, PK and DSAEK had significantly higher hazard ratios (HRs) than DMEK (HR = 13.6, 95% confidence interval [CI] [1.83, 101] for PK, 7.77 [1.03, 58.6] for DSAEK). Although not statistically significant, the HR estimate of nDSAEK to DMEK (HR = 7.64, 95% CI [0.98, 59.6]) indicated higher HR in nDSAEK than in DMEK. DMEK is the favorable option among the four surgical procedures to avoid graft rejection after keratoplasty., (© 2023. The Author(s).)

Tumor budding grade is a very useful histological prognostic indicator for colorectal cancer patients. Recently, it has been also reported as a significant prognostic indicator in invasive breast carcinoma patients. Our group and others have previously reported that the presence of a fibrotic focus in the tumor is a very useful histological finding for accurately predicting the prognosis in patients with invasive carcinoma of no special type (ICNST) of the breast. The purpose of the present study was to investigate whether a grading system incorporating tumor budding in a fibrotic focus is superior to the conventional grading system for tumor budding to accurately predict outcomes in patients with ICNST. According to our new grading system, we classified the tumors into grade I (164 cases), grade II (581 cases), and grade III (110 cases), and the results clearly demonstrated the significant superiority of the new grading system over that of conventional tumor budding alone for accurately predicting outcomes in patients with ICNST. Our findings strongly suggest that tumor cells and tumor-stromal cells interaction play very important roles in tumor progression rather than tumor cells alone., (© 2022. The Author(s).)