The gonio scratch study: methodology of a multicenter clinical trial establishing a new minimally invasive glaucoma surgery.

There are numerous surgical procedures for glaucoma. Minimally invasive glaucoma surgery is becoming popular; however, the disadvantage is the high incidence of anterior chamber hemorrhage. Heavy bleeding can also lead to increased intraocular pressure (IOP) postoperatively. Gonio scratch is a surgical procedure that improves aqueous humor outflow by rubbing off deposits on the trabecular meshwork with a Diamond Dusted Sweeper. As the conjunctiva and trabecular meshwork are not incised, no postoperative bleeding is expected, and the IOP spike will be minimal. We designed this study to determine the efficacy and safety of gonio scratch. This is an on-going multicenter, prospective, clinical trial. Patients who are scheduled for glaucoma surgery with or without cataract surgery are being enrolled. A total of 80 eyes will be recruited in the Hiroshima University Hospital, Miyoshi Eye Clinic, Yokoyama Retina Clinic, and Kusatsu Eye Clinic. All patients will undergo gonio scratch. When combined with cataract surgery, gonio scratch is performed after the intraocular lens is inserted. The primary study endpoint is the change in IOP from baseline to 1 year after surgery. The secondary endpoints are complications, number of glaucoma medications, surgical time, and changes in visual acuity and the visual field. This study protocol was approved by the institutional review board of Hiroshima University. The trial results will be shared with the scientific community at international conferences and by publication in a peer-reviewed journal. Trial registration number is jRCTs062200003.

Surgical Outcomes of Ab Interno Trabeculotomy Without Phacoemulsification.

Purpose: The aim of this study was to evaluate ab interno trabeculotomy outcomes without phacoemulsification. Methods: This retrospective study evaluated 118 eyes of patients aged 18 and above who underwent ab interno trabeculotomy between December 2017 and August 2022. When surgeries were performed in both eyes, only the eye undergoing the initial surgery was evaluated. Prior to and after surgery, the intraocular pressure (IOP) and mean number of IOP-lowering medications were compared. An IOP of ≤21 mmHg (A) and ≤18 mmHg (B) along with a ≥20% reduction in the preoperative IOP was defined as survival. Cases that required reoperation for glaucoma were defined as surgical failure. The Kaplan-Meier method was used to evaluate the survival rates. A Cox proportional hazards model was used to analyze the preoperative factors that influenced survival rates. Results: At 36 months postoperatively, the 13.4 ± 2.8 mmHg average IOP was significantly decreased from the preoperative 23.5 ± 9.8 mmHg value (P < 0.0001). Moreover, a significant decrease in the mean number of the IOP-lowering medications to 2.3 ± 1.4 at 36 months was found versus the initial 3.9 ± 1.1 preoperative value (P < 0.0001). The survival rates for criteria A and B at 36 months postoperatively were 28% and 25%, respectively. Only the preoperative IOP was identified by multivariate analysis as a factor influencing survival rates (P < 0.0001). Hyphema in 36 eyes (30.5%) and an IOP spike in 20 eyes (16.9%) were the only observed complications. Additional glaucoma surgery was required in 27 eyes (22.9%) during the follow-up period. Conclusion: Utilization of ab interno trabeculotomy effectively lowered the IOP and reduced the number of IOP-lowering medications. Patients with higher preoperative IOP exhibited better postoperative outcomes.

Effect of Ocular Dominance on Ocular Blood Flow Parameters.

PURPOSE: In binocular vision, there is a dominant eye and a nondominant eye, a phenomenon termed ocular dominance. This study determined the differences and associations of the ocular blood flow parameters between dominant and nondominant eyes in healthy Japanese subjects. METHODS: This cross-sectional study included 128 eyes of 64 subjects (13 male and 51 female) aged ≥ 20 years. The ocular blood flow parameters were assessed using laser speckle flowgraphy (LSFG), and software was used to calculate the mean blur rate (MBR), which reflects the blood flow velocity. RESULTS: There were no significant differences in axial length (AL), spherical equivalent (SE), intraocular pressure (IOP), uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), or ocular blood flow parameters between the dominant and nondominant eyes. The ocular blood flow parameters of the dominant eye were significantly and positively correlated with those of the nondominant eye (all P < 0.001). CONCLUSIONS: No significant differences in ocular blood flow parameters exist between the dominant and nondominant eyes in healthy subjects. The ocular blood flow parameters in the dominant eye are associated with those in the nondominant eye.

A Retrospective Study of Risk Factors Affecting Long-Term Outcomes Following Ab Interno Trabeculotomy and Goniotomy Concomitant with Phacoemulsification.

Purpose: To examine the potential risk factors affecting the long-term outcomes following a combination of phacoemulsification with ab interno trabeculotomy with the microhook (µLOT-Phaco) and goniotomy with the Kahook Dual Blade (KDB-Phaco). Methods: For 12 months, we retrospectively examined a total of 100 eyes of 100 patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (EG) who had previously undergone surgery between December 2016 and December 2020. Patients with a preoperative intraocular pressure (IOP) ˂12 mmHg were excluded. Probability of success was calculated using the Kaplan-Meier method, with surgical failure defined as an IOP >18 mmHg, <20% IOP reduction or additional glaucoma surgery. The Cox proportional hazards model was used to examine the potential risk factors for failure, which included age, gender, type of glaucoma, surgical techniques, preoperative IOP, number and type of preoperative IOP-lowering medications, preoperative visual field mean deviation (MD) value, and axial length. Results: For the 51 males and 49 females, mean preoperative age was 74.4 ± 9.0 years, with µLOT-Phaco performed in 44 and KDB-Phaco in 56 subjects. The type of glaucoma was POAG in 68 and EG in 32 eyes. Preoperative IOP was 20.5 ± 6.7 mmHg, while postoperative IOPs were 14.4 ± 4.2 mmHg, 13.7 ± 2.8 mmHg, and 14.6 ± 3.9 mmHg, respectively (P < 0.001). Significant decreases from the preoperative number of IOP-lowering medications (3.1 ± 1.2) were observed at 12, 24, and 36 months, respectively (1.2 ± 1.3, 1.6 ± 1.3, and 2.1 ± 1.4 (P < 0.001)). Probability of success at 12, 24, and 36 months postoperatively was 52.0%, 49.6%, and 47.7%, respectively. Lower preoperative IOP was shown to be a potential risk factor for surgical failure. Conclusion: Long-term follow-ups showed IOP decreased in µLOT-Phaco and KDB-Phaco patients. Results suggest that patients with higher preoperative IOP may have better postoperative outcomes.

Comparison of surgical outcomes between iStent inject W implantation and microhook ab interno trabeculotomy in combination with phacoemulsification in primary open-angle glaucoma patients.

Purpose: To examine primary open-angle glaucoma patients after undergoing combined cataract surgery with microhook ab interno trabeculotomy (µLOT-Phaco) or iStent inject W implantation (iStent-Phaco), and then evaluate the surgical outcomes after a minimum of 6 months of follow-up. Methods: Between October 2020 and July 2022, 39 µLOT-Phaco eyes and 55 iStent-Phaco eyes that underwent surgery were evaluated in this retrospective, multicenter comparative case series. Data that included preoperative and postoperative intraocular pressure (IOP), number of glaucoma medications, and occurrence of complications were collected from medical records and then examined. Surgical failure was defined as patients exhibiting a < 20% reduction in the preoperative IOP or an IOP > 18 mmHg on two consecutive follow-up visits, or when patients were required to undergo reoperation. Success rates were determined based on a Kaplan-Meier survival analysis. Results: At 3, 6 and 12 months postoperatively, there was a significant postoperative reduction in the IOP (p < 0.001) and in the medications scores (p < 0.001) for both of the groups. In the µLOT-Phaco and iStent-Phaco groups, the probabilities of success at 6 and 12 months were 55.3 and 45.5%, and 48.4 and 45.5% (p = 0.38; log-rank test), respectively. In the iStent-Phaco group, there was a significant decrease in the hyphema. Conclusion: Comparable surgical outcomes occurred for both the µLOT and iStent inject W procedures.

Ex-PRESS Implantation versus Trabeculectomy for Long-Term Maintenance in Patients with Open-Angle Glaucoma.

Purpose: To compare the efficacy of Ex-PRESS implantation (EXP) with that of trabeculectomy (TLE) with mitomycin C for maintaining low target intraocular pressure (IOP) in patients with open-angle glaucoma. Patients and Methods: Patients were randomly assigned to receive EXP or TLE. Surgical success was defined according to three target mean IOP ranges (5 mmHg ≤ IOP ≤ 18 mmHg [criterion A], 5 mmHg ≤ IOP ≤ 15 mmHg [criterion B], and 5 mmHg ≤ IOP ≤ 12 mmHg [criterion C]) representing reductions of at least 20% below the baseline on two consecutive follow-up visits 3 months post-surgery, with or without antiglaucoma medication and without further glaucoma surgery. Participants were divided into three subgroups based on baseline mean deviation (MD) values: early (MD ≥ -6 dB), moderate (-6 dB > MD ≥ -12 dB), and advanced (-12 dB > MD). Survival rates were calculated by subgroup. Results: A total of 73 patients, including 30 in the EXP group and 43 in the TLE group, were included in the study. No significant differences in baseline ocular or demographic characteristics were found between the two groups. No significant difference in IOP was noted every 6 months. After the 3-year follow-up, success rates were A) 60.0% and 60.2%, B) 45.7% and 58.1%, and C) 31.5% and 40.5% for the EXP and TLE groups, respectively. Moreover, there was no difference in success rate based on glaucoma level. Many glaucoma medications administered before surgery were associated with a higher failure rate in the TLE group but not in the EXP group. Conclusion: Both procedures resulted in similar IOP reductions and success rates for a low target IOP. The number of preoperative glaucoma medications was a risk factor for TLE failure.

Comparison of Corvis ST Parameters between Primary Open-Angle Glaucoma and Primary Angle-Closure Glaucoma.

BACKGROUND: We compared corneal visualization Scheimpflug technology (CST) parameters between eyes with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). METHODS: A retrospective analysis was performed on data from 89 eyes with POAG and 83 eyes with PACG that had CST examinations. CST parameters were compared between eyes with POAG and those with PACG using a linear mixed model (LMM). RESULTS: No differences were observed in age, central corneal thickness, intraocular pressure, or use of antiglaucoma eye drops between the two groups. Patients with PACG had a significantly shorter axial length (AL), a higher proportion of females, CST parameters, longer applanation 2 (A2) time, deeper A2 deformation amplitude, shorter peak distance, longer whole eye movement, and longer whole eye movement time than patients with POAG. The highest concavity (HC) length and PD showed a significant positive correlation with AL. However, A1 length, A1 deformation amplitude, A2 time, A2 velocity, A2 length, A2 deformation amplitude, HC time, whole eye movement, and whole eye movement time were negatively correlated with AL. CONCLUSIONS: The biomechanical properties of the cornea differed between POAG and PACG. In some parts, AL differences between the POAG and PACG groups might contribute to the variation in CST parameters.

Posterior sclerectomy for persistent serous retinal detachment with secondary glaucoma in Sturge-Weber syndrome: A case report.

INTRODUCTION: A serous retinal detachment is one of the most likely ocular manifestation of Sturge-Weber syndrome (SWS). This finding can frequently occur as a complication after filtering surgery to maintain the intraocular pressure (IOP). Proper treatment has been approached with choroidal hemangioma as an organ target. To the best of our knowledge, various treatments for SRD are associated with diffuse choroidal hemangioma has been approached. However, a second retinal detachment following radiation therapy has worsened the situation. Here, we report an unexpected serous retina and choroidal detachment after non penetrating trabeculectomy. Although radiation therapy has been proposed for previous detachment to the ipsilateral eye in this case, repetition radiation therapy was not suggested concerning the health and quality of life especially in for young subjects. However, the kissing choroidal detachment in this case necessitated immediate intervention. Thus, posterior sclerectomy was performed for the recurrent retinal detachment. We believe that an intervention for a SWS case related complication will remain a significant and important to share as a public health contribution. CASE PRESENTATION: A 20 year-old male confirmed with SWS with no known family history was diagnosed with SWS. He was gain from another hospital for glaucoma therapy. On the left brain MRI showed severe hemiatrophy in the frontal and parietal lobes and leptomeningeal angioma. Although his right (RE) eye had 3 gonio surgeries, 2 Baerveldt tube shunts and Micropulse trans-scleral cyclophotocoagulation, his IOP remained uncontrollable when he was 20 years old. RE IOP was in controlled after non-penetrating filtering surgery hence, his RE developed a recurrent serous retinal detachment. A posterior sclerectomy was performed in 1 quadrant of the globe to drain subretinal fluid. CONCLUSION: Sclerectomies to the inferotemporal quadrant of the globe for serous retinal detachment associated with SWS are considered efficient for optimal drain subretinal fluid, resulting in complete regression of detachment.

A multicenter phase II study on the safety of rho-kinase inhibitor (ripasudil) with needling for the patients after trabeculectomy.

Background: There is no established method of maintaining or reducing intra ocular pressure after the needling procedure for failing blebs post trabeculectomy. Regarding newer antihypertensive medications, ripasudil, which is a rho-associated protein kinase inhibitor ophthalmic solution, was able to prevent excessive scarring in vitro. This study aims to evaluate the safety of glaucoma patients submitted to the needling procedure and administered ripasudil for preventing scarring after the procedure. We also investigate the efficacy of ripasudil after needling for bleb failure through suppression of fibrosis to the bleb. Methods: This study is a multicenter, open-label, single-arm, phase II trial to evaluate the safety and efficacy of ripasudil in glaucoma patients after the needling procedure. Forty patients who will undergo needling at least 3 months after trabeculectomy will be recruited in Hiroshima university hospital and Hiroshima eye clinic. All the patients will instill ripasudil two times per day for three months after the needling procedure. The primary endpoint is the safety of ripasudil. Conclusions: We plan to establish the safety of ripasudil and to collect information involving the efficacy of ripasudil widely in this study.

Safety and Efficacy of the Rho-Kinase Inhibitor (Ripasudil) in Bleb Needling after Trabeculectomy: A Prospective Multicenter Study.

Ripasudil, a rho-associated protein kinase inhibitor ophthalmic solution, shows a protective effect in preventing excessive scarring in vitro. This study aims to evaluate the safety and efficacy of ripasudil for glaucoma patients submitted to the needling procedure. In this prospective, multicenter, single-arm study, we included 20 eyes of 20 patients with glaucoma who underwent the needling procedure without antimetabolites. All patients administered ripasudil after needling for three months. The primary endpoint of this study was the safety of ripasudil in patients, and the secondary endpoint was the change in IOP at 12 weeks after the needling procedure. No serious complications were found in the patients. One eye experienced pruritus and conjunctival follicle, while another eye had conjunctival follicle. These complications were transient and resolved quickly after discontinuation of ripasudil. The mean preoperative IOP was 14.6 ± 4.6 mmHg, which decreased to 11.0 ± 4.7 mmHg (p = 0.0062) at 1 week postoperatively. The IOP reduction effect continued to 12 weeks (11.8 ± 3.1 mmHg; p = 0.0448). The administration of the ROCK inhibitor, ripasudil, after the needling procedure is safe and effective in maintaining IOP for 12 weeks.

Usefulness of critical flicker fusion frequency measurement and its laterality for evaluating compressive optic neuropathy due to pituitary neuroendocrine tumors.

Critical flicker fusion frequency (CFF) is a short but sensitive method for evaluating optic nerve function. We measured CFF in patients with pituitary neuroendocrine tumors (Pit-NETs) to assess its usefulness. Data from 184 patients with nonfunctioning Pit-NETs, who had been treated with transsphenoidal surgery and had no medical history of eye diseases, was used in this retrospective study. Visual acuity decline (VAD) was defined as > 0.10 reduction in logMAR visual acuity and CFF decline (CFD) was defined as CFF value < 35 Hz. Visual field defect (VFD) was evaluated by automated perimetry on a Humphrey visual field analyzer. Potential associations between abnormal test results and tumor height from the suprasellar were analyzed. Contact between the optic nerve or chiasma and the tumor was present and absent in 161 and 23 patients, respectively. In patients showing contact, the difference in CFF between the left and right eyes was larger (p = 0.0008), and the optimal cutoff value using the receiver operating characteristic curve was 3 Hz. Therefore, ≥ 3 Hz was considered positive for CFF laterality (CFL), the most prevalent condition. Tumor height was lower in patients with CFL positivity compared to those with VAD or VFD (p < 0.01). The prevalence of test abnormalities was the highest for small tumors compared to those of other tests. Changes in CFL permit early detection of Pit-NETs. Our results indicate that CFF laterality can be seen in the early stages of compressive optic neuropathy due to Pit-NET.

Effect of the rho-kinase inhibitor ripasudil in needling with mitomycin C for the failure of filtering bleb after trabeculectomy: a cross-sectional study.

BACKGROUND: Rho-kinase inhibitors can inhibit fibrosis after glaucoma surgery. This study aimed to evaluate the effect of rho-kinase inhibitor after needling procedure with mitomycin C for the failure of filtering bleb with trabeculectomy. METHODS: This retrospective single-center study examined the effects of rho-kinase inhibitor after the needling procedure. We included 27 eyes of 27 patients with glaucoma who underwent needling procedure using mitomycin C and were subsequently treated with ripasudil-a rho-associated protein kinase inhibitor (ripasudil group)-or without ripasudil (control group). The ripasudil and control groups were compared in terms of intraocular pressure (IOP) and the number of antiglaucoma medications. Success at 12 months after the needling procedure was defined as a > 20% decrease in IOP from the preoperative period without surgical reintervention. RESULTS: At 12 months after the needling procedure, the mean IOP decreased from 16.9 ± 4.5 to 12.6 ± 1.1 mmHg in the control group and from 16.0 ± 5.3 to 12.2 ± 1.2 mmHg in the ripasudil group (p = 0.77). The 12-month success rates were 60.00% and 56.25% in the control and ripasudil groups (p = 0.98), respectively. In the preoperative period, the numbers of antiglaucoma drugs were 0.27 ± 0.46 and 0.92 ± 0.91 in the control and ripasudil groups (p = 0.022), respectively, and at 12 months after the needling procedure, they were 1.07 ± 1.44 and 0.73 ± 1.10 (p = 0.52), respectively. CONCLUSIONS: Treatment with ripasudil (a rho-associated protein kinase inhibitor) after the needling procedure with mitomycin C did not show better results than treatment with the mitomycin C needling procedure alone at 12 months after the procedure.

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.

Treatment outcomes in the neovascular glaucoma tube versus trabeculectomy study.

PURPOSE: To compare surgical outcomes between patients who underwent Baerveldt glaucoma implantation versus trabeculectomy (TLE) for the treatment of neovascular glaucoma. METHODS: We performed a prospective, randomized, controlled clinical trial at Hiroshima University and Tsukazaki Hospital, Japan. Patients were randomized to Baerveldt glaucoma implantation (23 patients) or TLE (27 patients). The primary outcome measure was the rate of intraocular-pressure control. Secondary outcome measures included complications and interventions. We defined "failure" as intraocular pressure ≥ 22 mmHg or < 20% reduction from baseline pressure, on two consecutive follow-up visits; need for additional glaucoma surgery; vision-threatening complications; or loss of light perception. Kaplan-Meier analysis was used to determine surgical success rates. Postoperative complications and interventions were compared between the two groups with Pearson Chi-square tests. RESULTS: There were no significant differences in demographic or ocular characteristics between the treatment groups at baseline. The postoperative follow-up was 26.6 ± 19.4 months in the Baerveldt group and 27.3 ± 20.1 months in the TLE group. There were no statistical differences (Mann-Whitney nonparametric tests with Bonferroni correction) in postoperative intraocular pressure measured at 6-month intervals. Success rates were 59.1 and 61.6% at 1-year after Baerveldt glaucoma implantation and TLE, respectively. Kaplan-Meier analysis showed no significant difference in success between groups (P = 0.71, log-rank test). Medication use, visual acuity, and interventions were similar between groups. Thirteen late postoperative complications developed in the Baerveldt glaucoma implantation group and four complications developed in the TLE group. Tube exposure was the most common late complication. CONCLUSION: These two procedures produced similar surgical success, intraocular-pressure reductions, visual acuity, and number of medications at the last visit. The TLE group showed smaller numbers of late complications and patients who lost more than two lines of visual acuity. Therefore, TLE might be a safer and better way to treat patients with neovascular glaucoma.

Comparison of the Humphrey Field Analyzer and Photopic Negative Response of Focal Macular Electroretinograms in the Evaluation of the Relationship Between Macula Structure and Function.

Purpose: To investigate the association between macular inner retinal layer thickness and macula visual field (VF) mean deviation as measured by the Humphrey Field Analyzer (HFA) or macular function as measured by focal macular electroretinograms (ERGs) in patients with glaucoma. Methods: The participants in this cross-sectional study were 71 patients with glaucoma and 10 healthy controls. Macular inner retinal layer thickness and function were measured in all participants using optical coherence tomography (OCT) and HFA or focal macular ERGs, respectively. Macular OCT images were segmented into the macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer/inner plexiform layer (GCL/IPL), and ganglion cell complex (GCC). Spearman correlation analysis was used to assess the relationship between macular inner retinal layer thickness and function. Results: Focal macular ERGs were composed of a negative wave (N1), a positive wave (P1), and a slow negative wave (N2). The N2 response density was significantly reduced in eyes with glaucoma, and was significantly associated with the thickness of the mRNFL (R = 0.317), GCL/IPL (R = 0.372), or GCC (R = 0.367). The observed structure-function relationship was also significantly correlated with the HFA VF mean deviation for each thickness [mRNFL (R = 0.728), GCL/IPL (R = 0.603), or GCC (R = 0.754)]. Conclusions: Although a significant correlation was found between the N2 response density and the thickness of the macular inner layer, the observed structure-function relationship with the mean deviation of the HFA VF was higher than that of the N2 response density.

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Determinants of corneal endothelial cell loss after sulcus placement of Ahmed and Baerveldt drainage device surgery.

AIM: In patients who underwent multiple intraocular surgeries, we evaluated determinants of decreased corneal endothelial cell density (CECD) after sulcus placement following Ahmed and Baerveldt drainage device surgery. METHODS: We retrospectively reviewed consecutive patients with glaucoma who underwent sulcus placement with an Ahmed glaucoma valve or a Baerveldt glaucoma implant. We compared presurgical and postsurgical CECD and risk factors for decreased CECD. RESULTS: We examined 41 eyes of 41 patients. Postsurgical CECD measurements were assessed 2.0±1.0 times during a median follow-up period of 28 months. The mean intraocular pressure (IOP) decreased from 28.4±11.6 mmHg to 12.2±5.3 mmHg 24 months after the operation. At 24 months, CECD decreased 14.6±5.4% after considering the variability in the number and time points of CECD determinations. History of prior surgery and higher preoperative IOP were significantly associated with a trend for a time-dependent decrease in CECD. CONCLUSIONS: Risk factors for decreased CECD after sulcus placement during Ahmed and Baerveldt drainage device surgery included the number of previous intraocular surgeries and higher presurgical IOP.

Effects of Study Population, Labeling and Training on Glaucoma Detection Using Deep Learning Algorithms.

Purpose: To compare performance of independently developed deep learning algorithms for detecting glaucoma from fundus photographs and to evaluate strategies for incorporating new data into models. Methods: Two fundus photograph datasets from the Diagnostic Innovations in Glaucoma Study/African Descent and Glaucoma Evaluation Study and Matsue Red Cross Hospital were used to independently develop deep learning algorithms for detection of glaucoma at the University of California, San Diego, and the University of Tokyo. We compared three versions of the University of California, San Diego, and University of Tokyo models: original (no retraining), sequential (retraining only on new data), and combined (training on combined data). Independent datasets were used to test the algorithms. Results: The original University of California, San Diego and University of Tokyo models performed similarly (area under the receiver operating characteristic curve = 0.96 and 0.97, respectively) for detection of glaucoma in the Matsue Red Cross Hospital dataset, but not the Diagnostic Innovations in Glaucoma Study/African Descent and Glaucoma Evaluation Study data (0.79 and 0.92; P < .001), respectively. Model performance was higher when classifying moderate-to-severe compared with mild disease (area under the receiver operating characteristic curve = 0.98 and 0.91; P < .001), respectively. Models trained with the combined strategy generally had better performance across all datasets than the original strategy. Conclusions: Deep learning glaucoma detection can achieve high accuracy across diverse datasets with appropriate training strategies. Because model performance was influenced by the severity of disease, labeling, training strategies, and population characteristics, reporting accuracy stratified by relevant covariates is important for cross study comparisons. Translational Relevance: High sensitivity and specificity of deep learning algorithms for moderate-to-severe glaucoma across diverse populations suggest a role for artificial intelligence in the detection of glaucoma in primary care.

The Relationship Between Corvis ST Tonometry Parameters and Ocular Response Analyzer Corneal Hysteresis.

PRECIS: Corvis ST Tonometry and Ocular Response Analyzer (ORA) measurements were conducted in primary open-angle glaucoma and normative subjects. Many parameters were significantly correlated, however, the strengths were weak to moderate. PURPOSE: Reichert ORA parameters are derived from pressure information following the application of air-jet, whereas detailed structural observation can be made using the Corneal Visualization Scheimpflug Technology instrument (CST). The purpose of the study was to investigate the association between CST measurements and ORA measured corneal hysteresis (CH). METHODS: Measurements of CST, ORA, axial length, average corneal curvature, central corneal thickness (CCT) and intraocular pressure with Goldmann applanation tonometry were carried out in 104 eyes of 104 patients with primary open-angle glaucoma and 35 eyes from normative subjects. The association between CST and ORA parameters was assessed using linear regression analysis, with model selection based on the second order bias corrected Akaike Information Criterion index. RESULTS: Deformation amplitude ratio (corneal softness, R=-0.51), SP A1 (corneal stiffness, R=0.41), and Inverse Radius (integrated area under the curve of the inverse concave radius, R=-0.44) were significantly correlated with CH (P <0.05). The optimal model to explain CH using CST measurements was given by: CH=-76.3+4.6×A1 time (applanation time in the corneal inward movement)+1.9×A2 time (second applanation time in the corneal outward movement) + 3.1 × highest concavity deformation amplitude (magnitude of movement of the corneal apex from before deformation to its highest concavity) + 0.016×CCT (R=0.67; P<0.001). CONCLUSIONS: CST parameters are significant, but weakly or moderately, related to ORA measured CH.

Relationship between novel intraocular pressure measurement from Corvis ST and central corneal thickness and corneal hysteresis.

AIMS: Corvis ST (CST) yields biomechanical corrected IOP (bIOP) which is purported to be less dependent on biomechanical properties. In our accompanied paper, it was suggested that the repeatability of bIOP is high. The purpose of the current study was to assess the relationship between intraocular pressure (IOP) measured with CST and central corneal thickness (CCT) and corneal hysteresis (CH), in comparison with IOP measured with Goldmann applanation tonometry (GAT) and the ocular response analyzer (ORA). METHODS: A total of 141 eyes from 141 subjects (35 healthy eyes and 106 glaucomatous eyes) underwent IOP measurements with GAT, CST and ORA. The relationships between IOP measurements (ORA-IOPg, ORA-IOPcc, CST-bIOP and GAT IOP) and biomechanical properties (CCT, CH and corneal resistance factor (CRF)) were analysed using the linear regression analysis. RESULTS: IOPg, IOPcc and GAT IOP were significantly associated with CCT (p<0.001), whereas bIOP was not significantly associated with CCT (p=0.19). IOPg, bIOP and GAT IOP were significantly associated with CH (IOPg: p<0.001; bIOP: p<0.001; GAT IOP: p=0.0054), whereas IOPcc was not significantly associated with CH (p=0.18). All of IOP records were associated with CRF (p<0.001). CONCLUSION: The bIOP measurement from CST is independent from CCT, but dependent on CH and CRF.