Human ocular thelaziasis with genetic analysis in Niigata Prefecture, Japan: A case report on an emerging zoonosis.

Purpose: We report the clinical findings and molecular identification of ocular Thelazia callipaeda from Niigata Prefecture in the Hokuriku area of Japan during winter. Observations: A 77-year-old male visited an ophthalmology clinic in Niigata Prefecture in January 2022 after a 2-week-duration of a conjunctival injection in the left eye and foreign body sensation. Slit-lamp microscopy revealed 11 active nematodes in the left conjunctival sac. Morphological characteristics included longer female body length than male, buccal cavity lacking teeth and lips, and serrated striations along the body surface. The specimens were determined to be T. callipaeda. Genetic analysis of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene revealed an h9 haplotype. Conclusions and Importance: T. callipaeda infection, especially the h9 haplotype, commonly occurs in western Japan owing to its higher incidence in warmer climates, suggesting the origin of the case. Here, we report a human case of Thelaziasis diagnosed in a cold region of Japan (the Hokuriku area) during winter. This human case of T. callipaeda infection from a cold, previously unassociated region, raises concerns about the potential geographical widening of its distribution, and further investigation may be warranted to prevent its spread.

Comparison of Schlemm's Canal Morphology Parameters Between Propensity Score-Matched Primary Open-Angle Glaucoma and Exfoliation Glaucoma.

Purpose: This study aimed to histologically compare the status of Schlemm's canal (SC) and Schlemm's canal endothelial (SCE) cells between trabeculectomy specimens from patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (EXG). Methods: A total of 182 eyes from 152 patients with POAG and 138 eyes from 116 patients with EXG underwent immunohistochemical staining for thrombomodulin. Equal numbers of cases were selected from both groups using propensity score matching. The following parameters were evaluated: total SC length, staining positive and negative SC length (PSC and NSC, respectively), opened and closed SC length, staining positive and opened SC length, staining positive and closed SC length, staining negative and opened SC length (NOSC), and staining negative and closed SC length. Results: After matching for age and gender, 87 cases were selected in each group. The EXG group had significantly higher preoperative IOP and medication scores. PSC was significantly longer in the POAG group, while NSC and NOSC were longer in the EXG group. Multiple regression analysis of these 174 cases revealed that PSC was significantly shorter in the EXG group. After matching for age, gender, preoperative IOP, and medication score, 64 cases were selected in each group, and NOSC was significantly longer in the EXG group. Conclusions: These findings suggest that in EXG, SCE loss occurs independently of background factors such as aging and medication use. The loss of SCE may have a more critical impact on IOP elevation in EXG compared to POAG.

The effects of the first versus second glaucoma drainage implant surgery in patients with primary open-angle glaucoma.

BACKGROUND: To investigate the outcome of non-valved glaucoma drainage implant surgery (GDIS) in primary open-angle glaucoma (POAG) patients divided in the first GDI group (patients who underwent the first GDIS) and the second GDI group (patients who underwent the second GDIS because of the failed first GDIS). METHODS: Intraocular pressure (IOP), visual acuity (VA), visual field defect (VFD), medication score (MS), survival rate of GDIS, complications, and patient background was retrospectively analyzed. Two success criteria were set: Criteria (1) IOP reduction ≥ 20% and 5 < IOP ≤ 21, Criteria (2) IOP reduction ≥ 20% and 5 < IOP ≤ 14. RESULTS: There were 136 eyes of 109 patients in the first GDI group and 32 eyes of 27 patients in the second GDI group. In the first GDI group and II, mean preoperative IOP was 26.7 ± 6.7 mmHg and 23.7 ± 3.5 mmHg, respectively (P = 0.09). No statistically significant difference in postoperative IOP reduction was found between the two groups (P = 0.39). At 5-years postoperative, the Criteria 1 (Criteria 2) survival rate in the first GDI group and the second GDI group was 60.4% (31.7%) and 61.2% (25.6%), respectively (Criteria 1: hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.30-1.35 [P = 0.24]; Criteria 2: HR: 0.81, 95% CI: 0.46-1.44, P = 0.48). No significant difference in VA, VFD change, MS, or complications was observed. Young patient age was the only significant factor for failure in the first GDI group (odds ratio: 0.95, 95% confidence interval: 0.91-1.00, P = 0.03). CONCLUSION: The second GDIS may be as effective as the first GDIS for IOP reduction in POAG patients, however, there is a high risk of failure in young-age patients and the surgery may be ineffective in eyes requiring Criteria 2.

Histological analysis of trabeculotomy - An investigation on the intraocular pressure lowering mechanism.

The primary aim of trabeculotomy (TLO) and/or minimally invasive glaucoma surgery (MIGS) is to produce a direct communication between the anterior chamber (AC) and collector channels (CC), which is believed to be the process by which intraocular pressure (IOP) is normalized. However, we previously reported our finding of the large opening of the Schlemm's canal (SC) into the AC in eyes with failed TLO (Amari et al., 2015). If the routes from the AC to the CC by TLO/MIGS are direct, IOP should be stabilized at around aqueous vein pressure if the SC and CC are undamaged. However, in eyes in which TLO/MIGS is successful, IOP usually stays at around the middle or high teens post surgery. In this current study, we retrospectively investigated the specific reason for middle- or high-teens IOP following TLO/MIGS via the histological examination of trabeculectomy (TRAB) specimens that include the area of previous TLO/MIGS in eyes with failed TLO or insufficient IOP control following TLO by specifically focusing on the behavior of the SC endothelium (SCE). Patient background, maximum IOP prior to TLO/MIGS and TRAB, the number medications administered, and elapsed time between TLO/MIGS and TRAB were reviewed. In 42 TRAB specimens of 31 120-180° TLO eyes (Group A; 27 ab-externo and 4 ab-interno eyes) and 11 360° suture TLO eyes (Group B), SC length (SCL), the site of the incision in the trabecular meshwork (TM) [i.e., the center (CEN)/anterior-tip (TIP)], and TM opening into the AC [i.e., open (OPN)/closed (CLS)] were histologically investigated. The correlation between the clinical parameters of the maximum IOP of pre-TLO/MIGS, the maximum IOP of pre-TRAB, the percentage of IOP reduction (PIR), and the histological results were statistically evaluated. Our findings revealed a significant negative correlation between the maximum IOP of pre-TRAB and SCL (P = 0.0167), and a significantly higher PIR in the eyes with OPN than those with CLS in Group A (P = 0.0045). However, no significant difference in SCL was found between the OPN and CLS eyes in both groups. In comparison to Group A, a higher percentage of OPN (82%) yet a smaller SCL (P = 0.0024) was observed in Group B. No significant correlation between clinical and histological parameters was found in Group B. In both groups, the common finding was sealing of the SC openings by SC endothelium (SCE) and no direct communication between the AC and the CC. This fact indicates that the nature by which SCE seals off the opened SC lumen into the AC created by TLO may be very important for maintaining the blood-aqueous barrier. Based on these results, we concluded that accessibility for aqueous humor to the SC and preservation of the SC may be important for lowering IOP by TLO. However, the opening of the SC into the AC (OPN type) does not guarantee an adequate IOP lowering effect if the SC is widely collapsed. Thus, TLO may be improved only by eliminating the most resistant part of the TM with minimal SCE damage.

Comparisons of Schlemm's canal and trabecular meshwork morphologies between juvenile and primary open angle glaucoma.

The histologic differences in Schlemm's canal (SC) and trabecular meshwork (TM), obtained from the trabeculectomy specimens of different age-group glaucoma patients, were compared. This study involved 44 trabeculectomy specimens of 37 juvenile-onset open-angle glaucoma (JOAG) patients (Group A) and 24 trabeculectomy specimens of 24 elderly-onset primary OAG (POAG) patients (age range: 70-79 years, Group B) with no familial history of POAG. Clinical parameters of gender, maximum intraocular pressure (IOP), and the number of glaucoma medications used prior to trabeculectomy were investigated and compared between the two groups. From light microscopy photographs of hematoxylin-eosin, and immunohistochemical staining of markers for SC endothelium (SCE), the total SC length (TSC), comprised of the opened-SC length (OSC) and the closed-SC length (CSC), the percentage of CSC in TSC (%CSC), the percentage of positive SCE marker in CSC (%PinCSC), and the percentage of negative SCE marker in OSC (%NinOSC) were analyzed. Moreover, podoplanin staining patterns in the TM were investigated and compared between the two groups. Among the clinical parameters, the mean maximum IOP in Group A (33.41 ± 9.24 mmHg) was the only significant parameter when compared to that in Group B (22.96 ± 7.17 mmHg, P = 0.000003). TSC in Group A was significantly shorter than that in Group B (P = 0.00092), and %CSC (P = 0.00004) and %PinCSC (P = 0.00342) in Group B were significantly higher than those in Group A. No statistically significant difference in %NinOSC was found between Group A and Group B (P = 0.76060). Juxtacanalicular tissue (JCT) in Group A showed compact and weak staining with podoplanin, while the JCT and closed-SC area in Group B showed intense staining. In the Group A subjects, TSC (P = 0.04819) and OSC (P = 0.02867) were significantly shorter in the non-familial cases than in the familial cases. Platelet coagulations 10-37 µm in size at the defect of the SCE in the inner wall of the SC were observed in 8 eyes (18%) and 4 eyes (17%) in Group A and Group B, respectively. The platelets appeared to repair the SCE damage for maintaining the blood aqueous barrier in both groups of POAG eyes. Smaller SC diameters and accompanying TM abnormality were features observed in the young-onset JOAG patients, thus suggesting developmental abnormalities in the outflow routes. The collapse of SC lumen, presumably due to aging, was the feature observed in the elderly-onset POAG patients. In Group A, the significantly higher IOP, despite of no significant number of topical medications used prior to trabeculectomy, also suggested that JOAG eyes can be categorized as a distinct type of POAG from the eyes of elder-aged POAG patients. The SCE drop out observed in the glaucomatous eyes of the different age groups suggested that worsening of IOP control may possibly occur equally in both groups.

Evaluation of the outcome of long-tube shunt implant surgery in uveitic glaucoma patients by analyzing the background of uveitis.

PURPOSE: To evaluate the efficacy of long-tube shunt surgery (LTSS) without valve in uveitic glaucoma (UG) eyes. METHODS: We retrospectively analyzed the data of 45 UG eyes that underwent only LTSS or LTSS combined with trabeculectomy (TLE) (LTSS/TLE). The UG eyes were analyzed by categorizing them into granulomatous/non-granulomatous, steroid responder/non-responder, and primary open-angle glaucoma (POAG) (POAG background)/non-POAG (non-POAG background). All granulomatous UG eyes received a continuous 3-times-daily administration of topical betamethasone post-LTSS. RESULTS: The eyes consisted of granulomatous (37 eyes, 82%)/non-granulomatous (5 eyes, 11%), steroid responder (19 eyes, 42%)/non-steroid responder (13 eyes, 29%), and 20 eyes with POAG or POAG background (p = 0.0022, 83%) among 24 cases of unilateral UG. The 5-year survival rates of only LTSS and LTSS/TLE were 66% and 100%, respectively. Kaplan-Meier survival-curve estimates in the non-granulomatous group were 100% for 6-year postoperative period, while the granulomatous group showed a gradual decrease along the 6-year (81%) postoperative period. The 5-year survival rates in the steroid responder group and the non-steroid responder group eyes were 74% and 78%, respectively. No intraocular pressure (IOP) elevation was observed in the positive steroid responder eyes post-LTSS. CONCLUSIONS: LTSS and LTSS/TLE were both effective in UG. Positive steroid response may be masked by LTSS in the positive responder eyes. Continuous administration of topical betamethasone post-LTSS may be important for preventing an IOP spike by suppressing inflammation in the anterior chamber. LTSS combined with TLE may be recommended in eyes with granulomatous UG, and the coexistence of a POAG/POAG background.

Novel homozygous in-frame deletion of GNAT1 gene causes golden appearance of fundus and reduced scotopic ERGs similar to that in Oguchi disease in Japanese family.

Background: The GNAT1 gene encodes the alpha-subunit of transducin in rod photoreceptors and is an important part of the phototransduction cascade. Defects in GNAT1 are very rare but have been identified in autosomal dominant and recessive congenital stationary night blindness (CSNB) and autosomal recessive rod-cone dystrophy. The purpose of this study was to determine the phenotype-genotype relationship in a non-consanguineous Japanese family with a GNAT1 mutation.Methods: Detailed ophthalmic examinations were performed on the patients and their family members. Whole exome sequencing (WES) was applied to the DNA obtained from the family members. Sanger sequencing and co-segregation analyses were performed to identify the most likely pathogenic variant.Results: Two female (13- and 11-years) and one male (15-years) patients from a family had night blindness from their childhood. The fundus had a mild golden appearance regardless of the state of light- or dark-adaptation. Electroretinographic (ERG) analyses showed that the scotopic a-wave was extinguished, and the mixed rod-cone responses were severely reduced with an electronegative form in patients. The shapes of the dark-adapted ERGs were similar to those recorded from patients with Oguchi disease. We identified a homozygous in-frame deletion c.818_820delAGA, p.Lys273del in the GNAT1 gene. Variants were verified by Sanger sequencing and co-segregated with the disease in five members of the family.Conclusions: Our findings indicate that a recessive GNAT1 mutation found in this family could be the cause of the golden appearance of the fundus and negative ERGs with reduced a-waves, and nearly absent b-waves in the mixed rod-cone ERGs.

A Histologic Categorization of Aqueous Outflow Routes in Familial Open-Angle Glaucoma and Associations With Mutations in the MYOC Gene in Japanese Patients.

Purpose: This study evaluated specific relationships between pathogenic mechanisms and genetic polymorphisms in primary open-angle glaucoma (POAG). We analyzed the morphologies of trabeculectomy specimens obtained from patients with familial POAG. Methods: We used light microscopy and transmission electron microscopy to examine specimens obtained from 17 eyes of 14 patients with familial POAG. We also conducted exome analyses of two families and used targeted Sanger sequencing to analyze samples obtained from the remaining patients. Results: The POAG cases examined in this study were divided into two groups based on morphologic characteristics. Group A eyes (7 eyes from 5 patients) had an abnormally thick trabecular meshwork (TM), whereas group B eyes (10 eyes from 9 patients) had a TM of normal thickness. The characteristics of the outflow routes in group A eyes were remarkable and included apoptotic TM cells, abnormally thickened TM basement membranes, fused TM beams, and occluded Schlemm's canals. All group A patients harbored mutations (F369L, P370L, T377M, and T448P) in the myocilin (MYOC) gene that were not found in group B patients. Conclusions: Although age matching of morphologic changes in the outflow routes was impossible due to the small sample size, this study suggests that abnormal TM cells may cause sequential damage in abnormally thickened TM basement membranes, TM cell apoptosis, TM beam fusion, and the occlusion of Schlemm's canals. The four detected MYOC mutations appeared to be associated with morphologic changes in the TM and the underlying pathogenesis of a subtype of familial POAG.

Long-term results of non-valved glaucoma drainage implant surgery and glaucoma drainage implant combined with trabeculectomy.

PURPOSE: The purpose was to investigate the efficacy and complications of nonvalved glaucoma drainage implant (GDI) surgery and GDI combined with trabeculectomy. SUBJECTS AND METHODS: Serial Japanese patients who received GDI were retrospectively investigated. The survival rate of eyes was analyzed using the Kaplan-Meier method, defining death as: (1) Intraocular pressure (IOP) <6 mmHg, or ≥22 mmHg, and <20% reduction of preoperative IOP, (2) additional glaucoma surgery, (3) loss of light perception. Prognostic factors of age, sex, previous surgery, type of glaucoma, synechial closure, preoperative IOP, type of GDI (single-, double-plate Molteno, Baerveldt 350) and GDI combined with trabeculectomy were investigated employing proportional hazards analysis. RESULTS: One hundred and twenty-four eyes of 109 patients aged 53.3 ± 7.8 years old were analyzed. Types of GDI were single-plate (15.3%), double-plate Molteno (71.8%), and Baerveldt 350 (12.9%). The results of survival rate analysis were 86.1, 71.1, 71.1, and 64.6% for 1, 3, 5, and 10 years respectively. Thirty-four eyes (27.4%) died because of uncontrolled IOP (19.4%), loss of light perception (5.6%), and additional glaucoma surgery (2.4%). Single-plate Molteno was the only risk factor for failure. Persistent unphysiological hypotony (0.8%) and bullous keratopathy (5.6%) were observed. CONCLUSION: Nonvalved GDI surgery and GDI combined with trabeculectomy using nonabsorbable tube ligature proved to be an excellent device for any type of glaucoma in Japanese patients. Hypotony and corneal endothelial loss are the most serious complication in the long-term results of our patients.

Effects of Vitrectomy on Recurrent Macular Edema due to Branch Retinal Vein Occlusion after Intravitreal Injection of Bevacizumab.

Purpose. To evaluate the effects of pars plana vitrectomy (PPV) on recurrent macular edema due to branch retinal vein occlusion (BRVO) after intravitreal injections of bevacizumab (IVB). Methods. This retrospective study included 22 eyes of 22 patients who underwent single or multiple IVB injections for macular edema due to BRVO and showed a recurrence of macular edema. All patients then underwent PPV and were followed up for more than 6 months after the surgery with examinations of best corrected visual acuity (BCVA) and optical coherence tomography (OCT). OCT parameters were central macular thickness (CMT) and average retinal thickness in a 1-mm-diameter circular region at the fovea (MRT). Results. Mean BCVA, CRT, and MRT were significantly improved from the baseline after PPV. Greater improvement of BCVA, CRT, and MRT was obtained after 1 month of IVB than after 6 months of PPV. No eyes showed worsening of macular edema after the surgery. Conclusion. PPV improved BCVA and recurrent macular edema due to BRVO, but PPV that was less effective than IVB had been in the same patients. PPV may be one of the treatment options for recurrent macular edema due to BRVO after IVB.