Real-world progression-free survival and overall survival of palbociclib plus endocrine therapy (ET) in Japanese patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer in the first-line or second-line setting: an observational study.

BACKGROUND: A recent large real-world study conducted in the United States reported the effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- advanced breast cancer (ABC). However, local clinical practice and available medical treatment can vary between Japan and Western countries. Thus, it is important to investigate Japanese real-world data. This observational, multicenter study (NCT05399329) reports the interim analysis of effectiveness of palbociclib plus ET as first-line or second-line treatment for HR+/HER2- ABC by estimating real-world progression-free survival (rwPFS) and overall survival (OS) in Japanese routine clinical practice. METHODS: Real-world clinical outcomes and treatment patterns of palbociclib plus ET were captured using a medical record review of patients diagnosed with HR+/HER2- ABC who had received palbociclib plus ET in the first-line or second-line treatment across 20 sites in Japan. The primary endpoint was rwPFS; secondary endpoints were OS, real-world overall response rate, real-world clinical benefit rate, and chemotherapy-free survival. RESULTS: Of the 677 eligible patients, 420 and 257 patients, respectively, had received palbociclib with ET as first-line and second-line treatments. Median rwPFS (95% confidence interval) was 24.5 months (19.9-29.4) for first-line and 14.5 months (10.2-19.0) for second-line treatment groups. Median OS was not reached in the first-line group and was 46.7 months (38.8-not estimated) for the second-line group. The 36-month OS rates for de novo metastasis, treatment-free interval (TFI) ≥ 12 months, and TFI < 12 months were 80.2% (69.1-87.7), 82.0% (70.7-89.3), and 66.0% (57.9-72.9), respectively. CONCLUSION: The addition of palbociclib to ET was effective for treating HR+/HER2- ABC in Japanese routine clinical practice.

Graft rejection episodes after keratoplasty in Japanese eyes.

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.

A large-scale clinicopathological and long-term follow-up study of solid papillary carcinoma of the breast.

Solid papillary carcinoma of the breast (SPC) is a rare tumor of the breast with the unique histology and frequent neuroendocrine differentiation. However, a real nature and diagnostic importance of the neuroendocrine differentiation have not been properly handled. And relationship between SPC and the other types of invasive breast carcinoma, especially neuroendocrine tumor of the breast (NETb), has not been fully explained. We conducted a clinicopathological study of SPC to tackle these problems.In the study, we included 127 cases of SPC with long-term follow-ups of up to 30 years. The incidence in the breast carcinoma was 2.0%. The patients with SPC had a significantly better prognosis and no patients died of the tumor. The 35 cases had only SPC in situ (SPC-IS), while the 92 cases had both SPC-IS and SPC with invasion (SPC-INV). Immunohistochemically, 123 of the 127 cases exhibited diffuse expression of one or more neuroendocrine markers. Fifty of the 92 cases had exclusively invasive SPC (iSPC) as the invasive component. Twenty-two cases of iSPC were combined with NETb and the 18 cases with MUC. Six of 8 cases with metastatic SPC-INV disclosed iSPC in the axillary lymph node.This study suggests that SPC is immunohistochemically compatible with NET of the systemic organs (NETs). And the unique morphology of SPC may represent a traditional histology of NETs. The study also indicates that SPC has close relationship between NETb and type B MUC. And SPC and NETb may represent a spectrum of the same disease.

Clinical Features of Glaucoma Associated with Cytomegalovirus Corneal Endotheliitis.

Purpose: 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.

Coincidence of Sarcoidosis and a COVID-19 vaccine-associated hypermetabolic lymphadenopathy in a patient with a history of invasive breast cancer: A case report.

Introduction and importance: Vaccine-associated hypermetabolic lymphadenopathy (VAHL) after a COVID 19 vaccination is a common adverse event and also a diagnostic challenge especially in patients with a history of a malignancy. Case presentations: A 47-year-old woman presented with enlarged lymph nodes in the right hilar, subcarinal, and right supraclavicular regions detected by computed tomography as a postoperative follow-up study of thyroid cancer. Fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) performed 3 weeks later revealed an FDG uptake in those swollen lymph nodes and in the novel lymphadenopathy in the left axilla and left subclavicular regions. Both biopsy specimens from the right supraclavicular and hilar lymph nodes revealed only multiple small granulomas with multinucleated giant cells without malignancy, consistent with sarcoidosis. The left axilla and subclavicular lymphadenopathy detected by the FDG-PET subsequently spontaneously regressed. Clinical discussion: The coincidental occurrence of VAHL and lymphadenopathy in sarcoidosis patients could cause diagnostic confusion especially in those with breast cancer. Conclusion: Sufficient attention should be paid both to the injection site and the time interval between the vaccination and imaging test in the era of nationwide mass vaccinations against COVID 19.

Intraoperative optical coherence tomography-guided nanothin Descemet stripping automated endothelial keratoplasty in a patient with a remarkably thickened cornea.

PURPOSE: To report use of intraoperative optical coherence tomography (OCT) for nanothin Descemet stripping automated endothelial keratoplasty (DSAEK) in a patient with an extremely thickened cornea due to advanced bullous keratopathy. OBSERVATIONS: A 90-year-old woman with a history of multiple trabeculectomies was referred to us for treatment of advanced bullous keratopathy (1400 µm central corneal thickness). Nanothin DSAEK was planned and performed. In brief, after the removal of the loose corneal epithelium, the anterior chamber was meticulously observed using a surgical microscope and oblique light via an endoillumination probe; however, the visibility of the anterior chamber was limited because of severe corneal edema. Subsequently, a nanothin (47 µm) DSAEK graft stained with trypan blue was inserted into the anterior chamber using an NS endoinserter. Intraoperative OCT was used successfully to visualize the graft unfolding, air tamponade, and graft attachment. At 3 months postoperatively, significant corneal clearing (625 µm central corneal thickness), improvement of visual acuity (decimal 0.04), and pain relief were obtained. CONCLUSIONS AND IMPORTANCE: Intraoperative OCT is useful for nanothin DSAEK even when the surgical microscope view is compromised by a remarkably thickened host cornea due to advanced bullous keratopathy. As an alternative to a penetrating keratoplasty, less invasive nanothin DSAEK was successfully performed.

Development of Cytomegalovirus Corneal Endotheliitis During Long-Term Topical Tacrolimus and Steroid Treatment for Chronic Ocular Surface Inflammatory Diseases.

PURPOSE: We report 3 cases of patients with chronic ocular surface inflammatory disease who developed cytomegalovirus (CMV) corneal endotheliitis during immunosuppressant and steroid treatment. PATIENTS AND METHODS: This is a retrospective observational study analyzing the clinical characteristics and outcomes of 3 patients with ocular surface inflammatory diseases (2 with Mooren ulcer and 1 with idiopathic scleritis) who developed CMV corneal endotheliitis. All patients developed CMV corneal endotheliitis between 8 and 14 months of starting steroid and immunosuppressant treatment, including topical 0.1% tacrolimus. Decimal visual acuity, endothelial counts, and intraocular pressure were analyzed. RESULTS: All patients received topical 0.5% ganciclovir after the diagnosis of CMV corneal endotheliitis, which improved endothelial inflammation. However, all patients developed irreversible mydriasis and required additional surgeries, including endothelial keratoplasty, cataract surgery, and glaucoma surgery. At the final follow-up (14-46 months post-CMV corneal endotheliitis onset), fair outcomes were achieved, as demonstrated by a mean decimal best-corrected visual acuity of 0.3 and a well-controlled intraocular pressure. CONCLUSIONS: Topical steroids and immunosuppressants can induce fulminant CMV corneal endotheliitis with cataract progression and irreversible mydriasis. In these cases, early diagnosis and treatment, including topical 0.5% ganciclovir, glaucoma surgery, cataract surgery, and endothelial keratoplasty, are necessary for preserving the patient's vision.

Long-term outcomes of Descemet stripping automated endothelial keratoplasty for bullous keratopathy after argon laser iridotomy.

PURPOSE: To report the long-term outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) for bullous keratopathy secondary to argon laser iridotomy (BK-ALI). STUDY DESIGN: Retrospective chart review. METHODS: Forty-five eyes from 41 consecutive patients with BK-ALI who underwent DSAEK from July 2007 to December 2013 were retrospectively analyzed. Best spectacle-corrected visual acuity (BCVA), endothelial cell density (ECD), and any complications were investigated over a 10-year postoperative period. RESULTS: The mean BCVA improved from 0.80 logMAR before DSAEK to 0.28 logMAR at 6 months after DSAEK; the mean values showed an additional slight improvement between 6 months and 10 years after the surgery (P < .01). The mean ECD decreased from 2864 cells/mm2 at baseline to 2269 cells/mm2 (20.8% loss) at 6 months post-DSAEK, and this decreasing trend continued throughout the 10 years after DSAEK (P < .01). The mean ECD was 1148 cells/mm2 (59.9% loss) after 5 years, and 568 cells/mm2 (80.2% loss) after 10 years. No graft deaths were observed throughout the 10-year period (5-year follow-up rate 60.0%, 10-year follow-up rate 20.0%). CONCLUSIONS: The 10-year outcomes of DSAEK for BK-ALI were excellent with a high graft survival rate.

Graft Edge Reflection of a Tightly Scrolled Roll Using Endoillumination as a Simple Method for Determining Graft Orientation in Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To describe a simple finding that can be used to determine donor tissue orientation in Descemet membrane endothelial keratoplasty (DMEK). This involves the appearance of a highly reflective round curved line from an overlapping graft edge within the anterior chamber using light from an endoilluminator. We here name this Kobayashi sign (K-sign). METHODS: Twelve consecutive eyes from 12 patients who underwent DMEK were evaluated for the presence of a K-sign. The presence of Berrospi sign (B-sign), a double-line reflection from the peripheral curls of the Descemet membrane (DM) roll that has been reported to be useful for correct graft orientation, was also evaluated. RESULTS: Of 12 cases, 3 donors showed a loosely scrolled roll soon after DM donor insertion; all 3 of these showed a positive B-sign only when the endoilluminator was used. Nine donors showed a tightly scrolled DM roll without a B-sign; among these 9 donors, a K-sign was visible in 7 cases only when the endoilluminator was used. The remaining 2 cases with a tight scroll configuration showed no K-sign even with the use of endoillumination, indicating that the roll edge was located completely downward; rotation of the roll using a small jet of fluid from paracentesis revealed K-sign in these cases. CONCLUSIONS: This technique is useful for determining the correct orientation of a tightly scrolled DM roll, subsequently enabling rapid DMEK surgery. For loosely scrolled DM roll, endoillumination enhanced B-sing is proven useful.

Clinical Evaluation of Electrolysis for Reis-Bücklers Corneal Dystrophies and In Vivo Histological Analysis Using Anterior Segment Optical Coherence Tomography.

PURPOSE: To report the effectiveness and clinical outcomes of corneal electrolysis for Reis-Bücklers corneal dystrophies (RBCDs) and provide in vivo histological analysis using anterior segment optical coherence tomography (AS-OCT). METHODS: A total of 7 patients with RBCD (2 male patients, 5 female patients; mean age, 50.0 years) from 3 pedigrees were enrolled in this prospective study. All patients underwent corneal electrolysis for decreased visual acuity or blurred vision. Changes in visual acuity, refraction, and corneal thickness were evaluated 1 month after electrolysis and statistically analyzed. Changes observed in AS-OCT images before and after electrolysis were qualitatively and quantitatively assessed. RESULTS: A total of 22 electrolysis procedures were performed on 7 patients during the median follow-up period of 10.7 years. Mean visual acuity significantly improved postoperatively, from 0.59 to 0.31 logarithm of the minimum angle of resolution (P = 0.013). Changes in refraction (from -2.42 to -2.12 D) and corneal thickness (from 570.8 to 577.6 µm) were not significant (P = 0.77 and P = 0.80, respectively). In all cases, assessment of AS-OCT images showed that the band lesion in Bowman's layer became less reflective after electrolysis. The mean thickness of the band lesion decreased from 101.5 to 88.3 µm (P = 0.002). CONCLUSIONS: Corneal electrolysis is an excellent treatment option for corneal opacities caused by RBCD. Corneal electrolysis improves visual acuity without changing corneal thickness or refraction. Therefore, repeat corneal electrolysis over the years might be a preferred long-term treatment strategy for RBCD. Moreover, AS-OCT is suitable for evaluating the effectiveness of this treatment and might be useful during postoperative follow-up.

In vivo Imaging of Reis-Bücklers and Thiel-Behnke Corneal Dystrophies Using Anterior Segment Optical Coherence Tomography.

PURPOSE: 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.

Visibility of the Retina Through an Air-Filled Anterior Chamber During Simultaneous Vitrectomy and Descemet's Stripping Automated Endothelial Keratoplasty.

PURPOSE: 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.

Clinical Evaluation of the "Lifeline Suture" Technique for DSAEK in Cases Without Posterior Capsule Using a Novel Donor Insertion Device.

PURPOSE: This study investigated preliminary clinical outcomes of a suture pull-through technique for Descemet stripping automated endothelial keratoplasty (DSAEK) termed the "lifeline suture" technique using a newly developed donor inserter (NS Endo-Inserter: NSI; Hoya Co, Ltd, Tokyo, Japan) in cases of bullous keratopathy without posterior capsule. METHODS: Six aphakic eyes without posterior capsule from 6 patients (mean age 73.8 ± 11.9 years) with bullous keratopathy were enrolled. DSAEK alone or as a vitreocorneal surgery was performed. Donor tissue was pulled into the anterior chamber using the NSI and a 9-0 polypropylene "lifeline suture" to prevent donor tissue from slipping into the vitreous cavity, which was removed at the end of surgery. Intraoperative and postoperative complications and 6-month postoperative central donor endothelial cell densities were measured and compared with preoperative values along with 6-month best-corrected visual acuity. RESULTS: All donors were successfully loaded into the NSI and then pulled into the anterior chamber using the lifeline suture. No intraoperative complications, graft dislocation, or primary graft failures were noted. Six months postsurgery, mean endothelial cell density was 2027 ± 747 cells/mm (mean loss 27.2 ± 28.1%) and mean best-corrected visual acuity improved to 0.31 decimal (P = 0.018). CONCLUSIONS: In this preliminary case series of bullous keratopathy without posterior capsule, DSAEK outcomes using the novel NSI donor inserter with lifeline suture were comparable or better than the results expected with conventional strategies. Thus, this technique enabled apparently safe DSAEK, preventing donor migration into the vitreous cavity while maintaining a stable anterior chamber, and is suitable for complex eyes including aphakia, lacking posterior capsule, or avitreal.

Clinical Evaluation of the NS Endo-Inserter, a Novel Donor Inserter for Descemet's Stripping Automated Endothelial Keratoplasty.

PURPOSE: This study investigated the clinical outcomes achieved with a newly developed donor inserter (NS Endo-Inserter [NSI], HOYA Co., Ltd., Tokyo, Japan) for Descemet's stripping automated endothelial keratoplasty (DSAEK) in Japanese eyes with bullous keratopathy secondary to argon laser iridotomy (BK-ALI). The NSI device utilizes pressure flow to push the DSAEK donor tissue into the anterior chamber. METHODS: Six eyes of 6 patients (1 male, 5 females; mean age, 78.5 years) with BK-ALI were enrolled. Donor tissue was pushed into the anterior chamber using the NSI. Intraoperative complications, graft dislocation, and iatrogenic primary graft failure were recorded for all eyes. Six-month postoperative central donor endothelial cell densities (ECD) were measured prospectively and compared with preoperative values, along with 6-month best corrected visual acuity (BCVA). RESULTS: In all cases, donor loading onto the NSI spatula and donor insertion into the anterior chamber using the NSI was smooth and successful; no intraoperative complications were noted. There were no cases of graft dislocation or IPGF. Postoperative ECD was 2,187.2 cells/mm2 (mean loss, 14.8%) and mean BCVA increased from 0.27 decimal to 0.8 at 6 months. CONCLUSION: In this small preliminary case series, clinical outcomes for patients with BK-ALI undergoing DSAEK using the NSI were comparable or better than those achieved with conventional DSAEK insertion techniques.

Changing indications and surgical techniques for keratoplasty during a 16-year period (2003-2018) at a tertiary referral hospital in Japan.

PURPOSE: 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.

Surgery-induced iris abnormalities after Descemet membrane endothelial keratoplasty and their impact on postoperative clinical outcomes.

Purpose: 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.

In vivo histology and p.L132V mutation in KRT12 gene in Japanese patients with Meesmann corneal dystrophy.

PURPOSE: To report genetic mutational analysis and in vivo histology of Meesmann corneal dystrophy. STUDY DESIGN: Prospective, case control study. METHODS: Six patients from three independent families with clinically diagnosed Meesmann corneal dystrophy were enrolled in this study. Slit-lamp biomicroscopy with fluorescein vital staining, anterior segment optical coherence tomography (AS-OCT), and in vivo laser confocal microscopy (IVCM) were performed on selected patients. Mutational screening for the keratin genes KRT3 and KRT12 was performed in all six patients and selected unaffected family members. RESULTS: Slit-lamp biomicroscopy revealed numerous intraepithelial microcysts in all affected individuals. AS-OCT revealed hyperreflectivity and high corneal epithelial layer thickness (mean, 64.8µm) in all individuals tested (3/3). By using IVCM, multiple epithelial microcysts and hyperreflective materials (6/6), subepithelial nerve abnormalities (6/6), tiny punctate hyperreflective material (6/6), and needle-like hyperreflective materials (4/6) were observed in the corneal stromal layer. A heterozygous genetic mutation in the KRT12 gene (c.394 C>G, p.L132V) was identified in all six patients. No pathological mutation was observed in the KRT3 gene. CONCLUSION: We identified a heterozygous genetic mutation (c.394 C>G, p.L132V) in the KRT12 gene in six Japanese patients with inherited Meesmann corneal dystrophy. This is the first study to confirm this genetic mutation in Japanese Meesmann corneal dystrophy patients. This mutation has been independently reported in an American Meesmann corneal dystrophy patient, confirming its pathogenicity. AS-OCT and IVCM proved to be useful tools for observing corneal epithelial layer pathology in this dystrophy. Furthermore, IVCM reveals corneal stromal layer pathological changes not previously reported in this dystrophy.

Development of a Donor Tissue Holding Technique for Descemet's Membrane Endothelial Keratoplasty Using a 25-Gauge Graft Manipulator.

PURPOSE: To report a modified surgical technique called the "donor tissue holding technique for Descemet's membrane endothelial keratoplasty (DMEK)" using a newly developed 25-gauge graft manipulator. METHODS: Six consecutive patients exhibiting endothelial dysfunction were enrolled and treated by DMEK. In brief, after insertion of a DMEK donor into the anterior chamber, the edge of the roll was grasped using a graft manipulator and this grasp was maintained throughout the centering and opening of the roll (holding technique). The following parameters were evaluated in comparison to the previous 10 consecutive DMEK cases in which the no touch technique was used: time of graft unfolding, incidence of intra-/postoperative complications, and best spectacle-corrected visual acuity (BCVA) and endothelial cell density (ECD) 6 months after the procedure. RESULTS: In both technique groups, neither intra- nor postoperative complications were noted in any case. No differences were observed between the two groups in postoperative BCVA (p = 0.88). Also, no differences were observed between the two groups in postoperative ECD (holding technique group: 2,108.3 cells/mm2, no touch technique group: 1,491.7 cells/mm2) (p = 0.08) Most notably, the time of graft unfolding prior to filling with air was significantly reduced in the holding technique group (305.5 s) compared to that of the no touch technique group (1,310.0 s; p = 0.01). CONCLUSIONS: This donor tissue holding technique enabled rapid and safe DMEK in a reproducible manner, even in Asian eyes with shallow anterior chambers with high vitreous pressure.

Combined Keratoplasty, Pars Plana Vitrectomy, and Flanged Intrascleral Intraocular Lens Fixation to Restore Vision in Complex Eyes With Coexisting Anterior and Posterior Segment Problems.

PURPOSE: To restore vision in complex eyes with coexisting anterior and posterior segment problems, combined corneal transplantation (penetrating keratoplasty [PK] or Descemet-stripping automated endothelial keratoplasty [DSAEK]), pars plana vitrectomy (PPV), and/or flanged intrascleral intraocular lens (IOL) fixation, designated vitreocorneal surgery are performed. In this study, we evaluated the usefulness of vitreocorneal surgery for eyes with complex comorbidities. METHODS: Thirteen consecutive eyes in 13 patients with coexisting corneal pathology (ie, corneal scarring, bullous keratoplasty, corneal laceration) and posterior segment pathology (ie, aphakia without capsular support, retinal detachment, intravitreal foreign body) underwent vitreocorneal surgery. Visual outcomes, intraoperative and postoperative complications, and additional surgery were retrospectively evaluated. RESULTS: Vitreocorneal surgery included PK + PPV + intrascleral IOL fixation (n = 5), PK + PPV (n = 3), PK + intrascleral IOL fixation (n = 1), DSAEK + intrascleral IOL fixation (n = 1), and DSAEK + PPV + intrascleral IOL fixation (n = 3). An intraoperative Eckardt temporary keratoprosthesis use enabled safe PPV. No vitreoretinal/IOL complications occurred. One eye required repeat DSAEK to repair endothelial graft detachment and inversion. In 3 eyes, secondary glaucoma was subsequently treated by glaucoma drainage device implantation through the pars plana. Mean best spectacle-corrected visual acuity (logMAR) improved from 1.8 ± 0.9 preoperatively to 1.1 ± 0.6 at 11.2 ± 14.6 months postoperatively (P = 0.002). Postoperative refraction was -0.68 ± 2.56 D (spherical equivalent). CONCLUSIONS: PK or DSAEK with PPV and/or flanged intrascleral IOL fixation is useful for complex eyes with coexisting anterior and posterior segment problems.

A 10-year review of underlying diseases for endothelial keratoplasty (DSAEK/DMEK) in a tertiary referral hospital in 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.