Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Glaucoma-Related Risk Factors for Endothelial Cell Loss and Graft Failure After Descemet's Stripping Automated Endothelial Keratoplasty.

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.

Deep Optic Nerve Head Structures Associated With Increasing Axial Length in Healthy Myopic Eyes of Moderate Axial Length.

PURPOSE: To elucidate which swept-source optical coherence tomography (OCT)-derived optic nerve head (ONH) parameters are associated with longer axial length (AXL) in healthy myopic eyes. DESIGN: Prospective cross-sectional observational study. METHODS: Two hundred eleven healthy eyes of 140 participants (96 emmetropic-mild myopic [AXL: 22.2-24.5 mm], 83 moderately myopic [24.5-26.0 mm], and 32 highly myopic [26.0-27.4 mm] eyes) were enrolled. Bruch membrane opening (BMO), anterior scleral canal opening (ASCO) area and ovality, minimum rim width, parameters defining misalignment between the BMO and ASCO planes, OCT-defined region of perineural canal retinal epithelium atrophy and externally oblique choroidal border tissue, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), circumpapillary choroidal thickness (cpChT), lamina cribrosa parameters, and peripapillary scleral (PPS) angle were calculated from BMO-centered radial scans reconstructed from 3D raster scans. Multivariate linear mixed models were used to elucidate ONH parameters that are independently associated with AXL. RESULTS: Longer AXL was associated with a greater misalignment between ASCO and BMO planes, larger region of externally oblique choroidal border tissue, thinner cpChT, larger PPS angle, larger ASCO area, and thicker cpRNFLT (all P < .040 after Bonferroni's correction for number of included explanatory variables). CONCLUSIONS: A greater misalignment between BMO and ASCO planes, thinner choroid, a more posteriorly bowed PPS, an enlargement of ASCO, and thicker cpRNFLT were each associated with longer AXL. An enhanced understanding of these AXL-associated configurations should provide essential information to improve our ability to detect glaucoma-induced ONH morphology in myopic eyes.

Ex-PRESS shunt combined with ab-interno peripheral iridectomy: A new surgical procedure for iridocorneal endothelial syndrome.

Purpose: Iridocorneal endothelial (ICE) syndrome may cause refractory glaucoma due to progressive synechial closure or membrane formation at the anterior chamber angle. Filtration surgeries are often required but are associated with a higher rate of surgical failure or complications than other types of glaucoma. Herein, we report a new and effective surgical procedure for glaucoma secondary to ICE syndrome: Ex-PRESS shunt combined with ab-interno peripheral iridectomy using a small-gauge vitreous cutter. Methods: Three patients with ICE syndrome who underwent surgery were included. Intraoperatively, an ab-interno peripheral iridectomy was performed using a small-gauge vitreous cutter through a corneal incision in the superior-nasal or superior-temporal quadrants to create space for the insertion of Ex-PRESS shunt free from the iris tissue. The shunt was inserted under the scleral flap. The first patient underwent combined cataract surgery, whereas patients 2 (pseudophakia) and 3 (phakia) underwent Ex-PRESS alone. Results: No intraoperative complications were observed. The intraocular pressure remained stable until the final postoperative visits at approximately 7, 4, and 1 year in Cases 1, 2, and 3, respectively. Case 2, with mild preoperative corneal edema due to graft failure in Descemet's stripping automated endothelial keratoplasty (DSAEK), underwent reDSAEK 6 months postoperatively. Conclusions and importance: Ex-PRESS shunt combined with ab-interno peripheral iridectomy using a small-gauge vitreous cutter may be a safe and effective surgical procedure in patients with ICE syndrome, regardless of the lens status.

Aldosterone as a Possible Contributor to Eye Diseases.

Aldosterone, an effector molecule of the renin-angiotensin-aldosterone system (RAAS), has been receiving more attention in the field of ophthalmology because of its possible role in the pathogenesis of various eye diseases or abnormalities; it may even become a target for their treatment. Primary aldosteronism, a typical model of a systemic aldosterone excess, may cause vision loss due to various ocular diseases, such as retinal vein occlusion, central serous chorioretinopathy, and, possibly glaucoma. RAAS components are present in various parts and types of cells present in the eye. Investigations of the local RAAS in various animal models of diabetic macular edema, retinal vein occlusion, retinopathy of prematurity, central serous chorioretinopathy, and glaucoma have found evidence that aldosterone or mineralocorticoid receptors may exacerbate the pathology of these disorders. Further studies are needed to elucidate whether the modulation of aldosterone or mineralocorticoid receptors is an effective treatment for preventing vision loss in patients with eye diseases.

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.

Cases with IgG4-related ophthalmic disease with mass lesions surrounding the optic nerve.

PURPOSE: IgG4-related ophthalmic disease (IgG4-ROD) is a lymphoproliferative disorder with representative symptoms including lacrimal gland enlargement (Mikulicz disease), masses around the trigeminal nerves, and extraocular muscle swelling. Herein, we describe cases of IgG4-ROD with lesions surrounding the optic nerve. METHODS: Of the 56 consecutive patients (35 men and 21 women) with a "definite case" of IgG4-ROD diagnosed from November 2004 through December 2019 at Kanazawa University hospital, seven patients presented with mass lesions around the optic nerve based on magnetic resonance imaging, and four patients showed symptoms of optic neuropathy. The clinical courses of these seven cases were reviewed. RESULTS: Among the 56 cases of IgG4-ROD, seven cases had lesions surrounding the optic nerve and all of these patients were male. The male dominance in the patient group with lesions surrounding the optic nerve was statistically significant based on a Chi-squared test (p < 0.001). Lacrimal gland swelling was also present in all seven cases, extraocular muscle enlargement in six cases, and trigeminal (infraorbital and supraorbital) nerve enlargement in six cases. Four patients showed deteriorated visual acuity compatible with optic neuropathy. These seven patients were treated by systemic steroid administration. Overall, in cases with optic neuropathy, visual function responded well to steroid therapy; however, recovery was limited in the worst case. CONCLUSIONS AND IMPORTANCE: Attention should be paid for mass lesions surrounding the optic nerve in patients with IgG4-related disease, especially in cases with high serum IgG4 levels.

Association of the CYP39A1 G204E Genetic Variant with Increased Risk of Glaucoma and Blindness in Patients with Exfoliation Syndrome.

PURPOSE: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation. DESIGN: Retrospective case study. PARTICIPANTS: A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort. METHODS: Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. MAIN OUTCOME MEASURES: Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation. RESULTS: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001). CONCLUSIONS: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation.

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.

Characterization of laser speckle flowgraphy pulse waveform parameters for the evaluation of the optic nerve head and retinal circulation.

To characterize laser speckle flowgraphy (LSFG) pulse waveform parameters for ocular circulation evaluation, a multicenter, prospective, cross-sectional study was conducted in 111 eyes of 86 healthy Japanese individuals. Optic nerve head (ONH) tissue-area, vessel-area mean blur rate (MT and MV, respectively), and MT and MV pulse waveform parameters were obtained using LSFG and ONH structural parameters using planimetry. Multivariate linear mixed-effects modeled regression analysis identified factors contributing to MT- or MV-waveforms using age, gender, smoking history, body mass index, systolic and diastolic blood pressure, heart rate, intraocular pressure, axial length, disc, rim, and ß-peripapillary atrophy areas, MT or MV, central retinal artery, and vein equivalents (CRAE and CRVE) as explanatory variables. MT- and MV-waveforms significantly correlated with one or more systemic factors, consistent with previous studies. Following confounding factor adjustment, MT-Skew significantly negatively correlated with ß-PPA area (P = 0.026); MT- and MV-flow acceleration index positively correlated with CRAE, MT, and MV (P = 0.041-< 0.001), compatible with these parameters' observed correlations to systemic factors. Significantly negative correlations of the blowout score and acceleration time index to CRAE partly conflicted with their correlations to systemic factors, and other waveform parameters showed little correlation to ocular factors. Thus, Skew and flow acceleration index assisted the in vivo ocular circulation characterization.

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.

Ocular and Systemic Factors Affecting Laser Speckle Flowgraphy Measurements in the Optic Nerve Head.

Purpose: To investigate the ocular and systemic factors related to glaucoma and to be adjusted for interindividual comparison of ocular blood flow measurement results by laser speckle flowgraphy (LSFG) obtained from the optic nerve head (ONH) in normal Japanese individuals. Methods: A multicenter, prospective cross-sectional study was conducted. The ONH tissue-area and vessel-area mean blur rate (MT and MV) were evaluated using LSFG and ONH structural parameters using planimetric methods. Multivariate linear mixed-effects modeled regression analysis was used to identify the contributing factors to the MT and MV. The explanatory variables were age; gender; smoking history; body mass index; mean arterial pressure (MAP); heart rate; intraocular pressure; axial length (AL); disc, rim, cup, and ß-peripapillary atrophy (ß-PPA) areas; and central retinal artery and vein equivalents. Results: In total, 195 eyes of 126 healthy individuals with an average age of 48.1 years were included. Multivariate analysis showed that MAP and disc area had a negative (P < 0.001) correlation, whereas ß-PPA area had a positive correlation with MT (P = 0.010). Age and AL had a negative correlation (P = 0.001 and P = 0.011, respectively), whereas cup area had a positive correlation (P = 0.012) with MV. Conclusions: Interindividual comparison of MT or MV must be adjusted for both systemic factors (blood pressure or age) and local ocular factors (AL and disc, cup, or ß-PPA area). Translational Relevance: Our results provided reference data on the LSFG measurement and are important in comparing ocular blood flow between individuals using LSFG.

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.

The association of primary aldosteronism with glaucoma-related fundus abnormalities.

PURPOSE: To elucidate glaucoma-related fundus abnormalities in patients with primary aldosteronism (PA). METHODS: The study compared 272 eyes from 137 PA patients and 352 eyes from 177 control subjects selected randomly from 1173 participants of a public glaucoma screening. The presence of glaucomatous optic disc appearance (rim thinning and cup enlargement) and retinal nerve fiber layer defects (RNFLDs) was determined independently from fundus photographs. The results were compared between the PA and control groups. RESULTS: There were 9 patients (6.6%) with glaucomatous optic disc abnormalities in the PA group and 10 cases (5.6%) identified in the control group (p = 0.92). RNFLDs were detected more frequently in the PA group (55 eyes, 20.2%) than in the control group (26 eyes, 7.4%; p<0.001). The two types of RNFLDs were classified as either having their central ends at the disc margin (D) or away from the disc margin and around the retinal vessels (V). Type D and V RNFLDs were detected in 35 (12.9%) and 26 (9.6%) eyes in the PA group and in 25 (7.1%) and 4 (1.1%) eyes in the control group, respectively. Both types of RNFLDs were more frequent in the PA group than in the control group (Type D and V, p = 0.03, <0.001, respectively). CONCLUSION: Although the prevalence of glaucomatous optic disc appearance did not differ between the two groups, RNFLDs were more frequent in PA patients than in the control group. Moreover, RNFLDs with their central ends located around retinal vessels were characteristic of PA patients.

iStent Trabecular Micro-Bypass Stent Implantation with Cataract Surgery in a Japanese Glaucoma Population.

INTRODUCTION: This study assesses two-year efficacy and safety following implantation of a single trabecular micro-bypass stent (iStent®) with concomitant phacoemulsification cataract surgery in Japanese patients with open-angle glaucoma (OAG). MATERIALS AND METHODS: This retrospective, consecutive case series included eyes that underwent iStent implantation with phacoemulsification and were followed for 24 months postoperative. Efficacy and safety measures included intraocular pressure (IOP), number of glaucoma medications, adverse events, secondary surgeries, visual fields, and endothelial cell counts. RESULTS: Of 73 operated eyes, 53 eyes had 24 months of follow-up and are analyzed. Diagnoses included primary open-angle glaucoma (POAG, n=25), normal-tension glaucoma (NTG, n=16), and pseudoexfoliative glaucoma (PXG, n=12). At 24 months, mean IOP reduced by 18% to 13.6±3.0 mmHg versus 16.5±3.4 mmHg preoperatively (p<0.0001), and mean medication number reduced by 81% to 0.37±0.74 versus 1.96±0.98 preoperatively (p<0.0001). The percentage of medication-free eyes was 77% versus 0% preoperatively, and 81% of eyes had IOP ≤15 mmHg versus 42% preoperatively. Results were similarly favorable across glaucoma subtypes (POAG, NTG, PXG). Notably, mean IOP in NTG eyes decreased to 12.8±1.4 mmHg from 14.4±3.0 mmHg preoperatively (p=0.03), and medications decreased by 87% to 0.31±0.70 versus 2.38±0.72 preoperatively (p<0.0001). At 24 months, 81% of NTG eyes were medication-free (versus 0% preoperatively); 2 NTG eyes (13%) were on ≥2 medications (versus 100% preoperatively). Throughout the follow-up, visual fields and endothelial cell counts remained stable; 1 eye (1.9%) underwent filtration surgery. DISCUSSION: Favorable safety and significant IOP and mediation reductions were achieved through two years following iStent implantation with phacoemulsification in a Japanese population. These gains were achieved across all glaucoma subtypes (including POAG, NTG, PXG). CONCLUSION: This real-world study supports the viability of iStent implantation to treat Japanese patients with glaucoma and shows that the benefits extend to those with NTG or PXG in addition to POAG.

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.

Visualization of the Retina in Intact Eyes of Mice and Ferrets Using a Tissue Clearing Method.

Purpose: Visualization of specific cells and structures in intact organs would greatly facilitate our knowledge about pathological changes; therefore, a tissue clearing method applicable to the intact eye may be valuable. Here we report a novel imaging method for the retina using the hyperhydration-based tissue clearing technique CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational Analysis). Methods: Eyes of Institute of Cancer Research (ICR) mice, C57BL/6 mice, and normally pigmented sable ferrets (Mustela putorius furo) were used. Intact eyes were subjected to CUBIC, melanin bleaching with H2O2, and immunostaining. Images of the retina in intact eyes were taken using epifluorescence microscopes and confocal microscopes. Results: The combination of melanin bleaching and CUBIC efficiently made the eyes of C57BL/6 mice transparent. By combining melanin bleaching, CUBIC, and immunostaining, we succeeded in visualization of retinal structures from the outside of the intact eyes of mice. Furthermore, we found that our methods were applicable not only to mouse eyes but also to ferret eyes, which are much larger than those of mice. Conclusions: Our method was useful for visualizing specific cells and structures in the retina of intact eyes with single-cell resolution without making tissue sections. Translational Relevance: This simple and efficient method can be applicable to various rodent models, including those associated with glaucoma or myopia, and will facilitate evaluating the effects of novel therapy for relevant eye diseases by visualizing changes from the retina to the sclera at both molecular and macroscopic levels simultaneously in a whole-eye preparation.

Effectiveness of trabeculectomy with mitomycin C for glaucomatous eyes with low intraocular pressure on treatment eye drops.

PURPOSE: To examine the efficacy and safety of current trabeculectomy with mitomycin C in Japan for glaucomatous eyes with low intraocular pressure (IOP). METHODS: Two hundred ninety-four eyes of 294 patients with IOP ≤21 mmHg before surgery were studied; all patients were participants in the Collaborative Bleb-related Infection Incidence and Treatment Study (CBIITS), a multicentre, prospective, cohort study conducted at 34 ophthalmological institutions throughout Japan. All eyes had an intraocular pressure ≤ 21 mmHg and had undergone trabeculectomy alone or phacotrabeculectomy. Two success criteria were used: Criterion A comprised 20% reduction of baseline IOP and Criterion B comprised 30% reduction of baseline IOP. The primary outcome was the success rate for each of these criteria. RESULTS: The qualified success rates were 87.3% for Criterion A and 42.0% for Criterion B at 5 years. Mean IOP was significantly reduced, from 16.7 ± 2.7 to 11.6 ± 4.0 mmHg at 5 years after trabeculectomy (p < 0.0001); the number of anti-glaucoma medications significantly decreased from 2.7 ± 1.1 to 1.0 ± 1.2 (p < 0.0001) at 5 years after the surgery. Three or more trabeculectomies, and needling were related to increased risk of failure. Incidences of postoperative hyphema, infection, shallow anterior chamber and bleb leakage were 2.4%, 2.4%, 2.0% and 3.4%, respectively. CONCLUSIONS: This study showed that trabeculectomy with mitomycin C is an effective procedure with few surgical complications for reducing IOP in patients, even if preoperative IOP was within the normal range.

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.

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.