Teruhiko Hamanaka

Histopathology of the trabecular meshwork and Schlemm's canal in primary angle-closure glaucoma.

PURPOSE To investigate the detailed histopathology of trabecular meshwork changes associated with primary angle closure glaucoma (PACG). METHODS Thirty trabecular blocks obtained from trabeculectomy (TLE) of 25 PACG patients were embedded in paraffin for immunohistochemical staining of thrombomodulin, CD68, D2-40, and epon for transmission electron microscopy. Eleven TLE blocks obtained from normal-tension glaucoma patients were used as a control. Histologic changes of outflow routes were analyzed by comparing the existence of iridotomy, gonioscopy-evaluated angle closure, intraocular pressure (IOP), episodes of acute attack, visual field defect classified by Aulhorn-Greve, anterior chamber depth, lens thickness, and axial length. RESULTS Occlusion of the Schlemms canal (SC) of <150 μm was observed in 11 eyes, which significantly correlated with gonioscopy-evaluated angle closure (T = 19.33 > χ² (f,α) = 9.488). Moderate correlation between SC occlusion and IOP before TLE was also observed (correlation coefficient: -0.540). Slightly negative or no correlations were found between SC occlusion and the other parameters. Thinned SC endothelium at the junction or degenerated SC endothelium and various degrees of SC occlusion and fusion of the trabecular beams where trabecular cells degenerated with damaged mitochondria were the general findings in the PACG eyes involved in this study. CONCLUSIONS Persistent trabecular-iris contact or peripheral anterior synechia may block aqueous outflow resulting in a progressive process of SC endothelial damage and subsequent SC occlusion, as well as trabecular cell damage possibly due to impairment of mitochondrial function and subsequent fusion of the trabecular beams. These changes may be the reason for residual glaucoma after laser iridotomy or cataract surgery.

Bleb analysis by using anterior segment optical coherence tomography in two different methods of trabeculectomy.

PURPOSE To investigate the correlation between bleb morphology and IOP control via the modified Indiana Bleb Appearance Grading Scale (IBAGS) and anterior-segment optical coherence tomography (AS-OCT) in two different trabeculectomy (TLE) groups. METHODS This study involved 94 eyes with primary open angle glaucoma that underwent two different TLE methods: limbal-based TLE (group I, 62 eyes) and fornix-based TLE (group II, 32). IOP control was defined as successful with an IOP ≤ 20 mm Hg and ≥20% reduction of preoperative IOP. IBAGS and various parameters of the bleb height, extent, wall thickness, ciliochoroidal detachment (CCD), and lake under the scleral flap (LUSF) were obtained by slit-lamp and AS-OCT, respectively. Correlation between IOP control and IBAGS/AS-OCT parameters were assessed by SAS. RESULTS Both groups had the same success rate. As to correlation between IOP control and IBAGS, extent and Seidel were the best-paired parameters in group I (Cp = 3.0402, R = 0.6401), yet no parameter was significant in group II (maximum R = 0.1599). As to correlation between IOP control and AS-OCT, the combinations of height, extent, and the minimum value of bleb wall thickness were significant (Cp = 0.2037, 0.2314, R = 0.4336, 0.4330) in group I. In group II, no parameter was significant, except CCD and/or LUSF (P = 0.032). As to coincidence of IBAGS and AS-OCT parameters, height and extent in group I (P = 0.000, P = 0.000) and height in group II were statistically significant (P = 0.020). CONCLUSIONS IOP control in limbal-based TLE seemed to be more dependent on the large size and thinned-wall bleb than that in fornix-based TLE.

Involvement of Platelet Coagulation and Inflammation in the Endothelium of Schlemm's Canal

PURPOSE To investigate whether the endothelial cells of Schlemms canal (ECSCs) are connected to lymphatic vessels or are involved in platelet coagulation and inflammation, by comparing them to lung tissue cells. METHODS Three normal eyes, trabeculectomy specimens of 6 early-onset primary open-angle glaucoma (POAG), 15 late-onset POAG, and 6 normal-tension glaucoma (NTG), and lung tissues from 10 normal autopsy cases were used. The specimens were processed for light microscopy of immunohistochemical staining. The antibodies used in this study were von Willebrand factor (vWF) and thrombomodulin for evaluating the platelet coagulation system, CD 34 as a marker for blood vessels, platelet/endothelial cell adhesion molecule (PECAM-1) and E-selectin for evaluating the involvement of inflammation, and D2-40 as a marker for lymphatic vessels. RESULTS Thrombomodulin, CD 34, PECAM-1 and E-selectin were detected in ECSCs, the endothelial cells of Sondermanns canal, and the endothelial cells of alveolar capillaries in the lung (EACL), whereas vWF was negative in those cells. Sondermanns canal was often found in compact juxtacanalicular tissue (JCT) in eyes with early-onset POAG. D2-40 was positive in the endothelial cells of lymphatic vessels in the lung (ELVL) and trabecular cells. In early-onset POAG, trabecular cells in JCT were mostly negative for D2-40. CONCLUSIONS ECSCs and EACLs are suggested to have developed specifically for their functions from the aspects of the anti-platelet coagulation system and may be involved in inflammation for leukocyte infiltration. D2-40 and thrombomodulin seem to be useful for evaluating morphologic abnormality in POAG.

Morphological Abnormalities of Schlemm's Canal in Primary Open-Angle Glaucoma From the Aspect of Aging

PURPOSE To evaluate morphological abnormalities of Schlemms canal (SC) among primary open-angle glaucoma (POAG) patients with a family history of POAG (group A), those without a family history of POAG (group B), and patients with normal-tension glaucoma (group C) from the aspect of aging. METHODS A total of 160 trabeculectomy specimens from 133 POAG patients were processed for light microscopy using immunohistochemical staining of thrombomodulin and transmission electron microscopy. The following parameters were statistically evaluated: SC length, the percentage of the thrombomodulin-negative area (PTNA) of SC, and the inner-wall SC endothelial cell density (SC-ECD/100 μm). RESULTS No significant differences in age were observed among the three groups (group A: 56.71 ± 14.83; group B: 58.13 ± 18.13; group C: 56.61 ± 9.78). Length of SC in the group A patients (198.70 ± 81.65 μm, n = 70 eyes) was significantly shorter than in group B (250.30 ± 70.83 μm, n = 67 eyes), and group C (277.70 ± 65.52 μm, n = 23 eyes) patients. A positive correlation of patient age and SC length was observed in group B (r = 0.45, P = 0.0013), but SC length in group A tended to decrease with aging (r = -0.22, P = 0.07). No significant difference in SC was found between group A and B patients before age 50 years (P = 0.30). Correlations between patient age and increase of PTNA (r = 0.38, P = 0.0013) and patient age and decrease of SC-ECD (r = -0.53, P = 3.95 × 10(-6)) were observed only in the group B cases. CONCLUSIONS Our findings suggest that SC in group A may easily collapse during middle age, while SC in group B remains open and SC endothelial cells drop out at around middle age.

Pathologic investigation failure of trabeculotomy.

Purpose:To investigate the reason for failure of trabeculotomy using trabeculectomy (TLE) specimens involving the area of previous trabeculotomy. Materials and Methods:Thirteen TLE specimens from 13 patients with open-angle glaucoma were processed for transmission electron microscopy and light microscopy, involving immunohistochemical staining of thrombomodulin, D2-40 (podoplanin), and CD34. Results:All intraocular pressure after trabeculotomy decreased to normal and then returned to the same or a higher level compared with that before TLE. Eleven and 2 TLE specimens were taken from areas with no peripheral anterior synechia (PAS) and PAS areas, respectively. The 4 types of histologic change in the trabecular meshwork were observed: (1) persistence of a disconnected trabecular meshwork with swelling or degeneration at the cut edge; (2) fusion of the trabecular meshwork; (3) a membrane covering the innermost trabecular meshwork; and (4) pigmented cell invasion into the disconnected trabecular meshwork at the PAS site. Schlemm canal (SC) opening into the anterior chamber and SC occlusion were observed in 2 and 8 eyes, respectively. Conclusions:Opening of SC into the anterior chamber observed in the eyes with failed trabeculotomy suggested that the enhancement of conventional routes may not be important for the intraocular pressure-lowering effect. All 4 types of histologic change in the trabecular meshwork, as mentioned above, may reduce enhancement of the newly created unconventional routes by trabeculotomy.

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.

Atopic Glaucoma: Clinical and Pathophysiological Analysis.

Purpose:Open-angle glaucoma associated with severe atopic dermatitis (atopic glaucoma) tends to be severe and difficult to treat because of ocular surface/eye lid inflammation. To determine the validity of regarding atopic glaucoma as a clinical entity, we carried out retrospective analysis and pathologic investigations. Materials and Methods:Forty-five cases (62 eyes) of atopic glaucoma were reviewed retrospectively. During surgical treatment, aqueous humor and trabeculectomy specimens were obtained. The aqueous humor samples were analyzed by multiplex cytokine assay. The surgical specimens were analyzed histologically. Results:Atopic glaucoma was often associated with atopic cataracts (43 eyes) and retinal detachments (19 eyes). A history of glucocorticoid medications was absent in 12 cases. A total of 50 eyes required surgical interventions because of advanced visual field defects and/or high intraocular pressures. Bleb-associated postsurgical infections were observed in 7 eyes. Elevated levels of inflammatory cytokines (IL-8 and CCL2) were observed in the aqueous humor samples obtained from atopic glaucoma patients compared with those from senile cataract patients. Ultrastructural analysis of trabecular meshwork tissues obtained from atopic glaucoma patients showed abnormal accumulation of 10 to 30 nm fibers in the corneoscleral meshwork. Conclusions:We would like to propose atopic glaucoma as a new clinical entity, ranging from pure atopic glaucoma to a mixed type of atopic/steroid-induced glaucoma that should be considered as one of the clinical features of atopic ocular complications.

Bilateral neovascular glaucoma due to multicentric Castleman disease

We immediately discontinued the administration of latanoprost and started application of topical diclofenac sodium four times daily. Four months later, visual acuity in his right eye improved from 0.7 to 1.2, and the micropsia disappeared. Although the retinal capillary telangiectasis was essentially unchanged, slit-lamp biomicroscopic fundus examination showed that the macular edema was improved, and OCT showed a decrease in the retinal thickness (Fig. 2B).

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 Schlemms 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 Schlemms 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.

Acute Onset Secondary Pigmentary Glaucoma Followed by Second Intraocular Lens Implantation in a Patient with Atopic Dermatitis

A 36-year-old man underwent trabeculectomy in his right eye because of sudden onset open angle glaucoma (intraocular pressure (IOP): 48 mmHg) 11 months after the implantation of a second intraocular lens (IOL).