Figure 1.
(A,B) Images of the right eye of Case 53, a 50-year-old female in Group III with a max intraocular pressure (IOP) of 14 mmHg. Photographs of fluorescein gonio angiography (FGA) and fundus fluorescein angiography (FFA) mounted on a transparent sheet showing different zones (B) and slit-lamp gonioscopy (A, inset). A nodule can be seen at the ciliary body band (black arrowhead in A, inset). No topical betamethasone was prescribed prior to FGA and gonioscopy. The corresponding areas in A and A, inset are indicated by white and red arrowheads. Angle NVs can be seen arising perpendicularly from the iris root, and then changing their direction and running circumferentially along the trabecular meshwork; (B) Panoramic FFA image showing no non-perfusion area. The patient has had no recurrence of inflammation in both eyes for 18 years; (C) Fundus-camera images of FGA in the left eye of Case 23, a 72-year-old male in Group I with a max IOP of 35 mmHg. (C, inset) Slit-lamp image showing no nodule. Topical betamethasone had been irregularly prescribed. The corresponding areas in C and C, inset are indicated by white and red arrowheads.
Figure 1.
(A,B) Images of the right eye of Case 53, a 50-year-old female in Group III with a max intraocular pressure (IOP) of 14 mmHg. Photographs of fluorescein gonio angiography (FGA) and fundus fluorescein angiography (FFA) mounted on a transparent sheet showing different zones (B) and slit-lamp gonioscopy (A, inset). A nodule can be seen at the ciliary body band (black arrowhead in A, inset). No topical betamethasone was prescribed prior to FGA and gonioscopy. The corresponding areas in A and A, inset are indicated by white and red arrowheads. Angle NVs can be seen arising perpendicularly from the iris root, and then changing their direction and running circumferentially along the trabecular meshwork; (B) Panoramic FFA image showing no non-perfusion area. The patient has had no recurrence of inflammation in both eyes for 18 years; (C) Fundus-camera images of FGA in the left eye of Case 23, a 72-year-old male in Group I with a max IOP of 35 mmHg. (C, inset) Slit-lamp image showing no nodule. Topical betamethasone had been irregularly prescribed. The corresponding areas in C and C, inset are indicated by white and red arrowheads.
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Figure 2.
(A,B) Images of the right eye of Case 46, a 73-year-old female in Group III with a max IOP of 47 mmHg. Photographs of FGA (A) and panoramic FFA (B) mounted on a transparent sheet indicating different zones. (A, inset) Slit-lamp gonioscopy image showing bleeding, possibly from angle NV at the same area as that of FGA. Angle NV observed by FGA showing dot fluorescein staining (arrowhead in A) and leakage (arrows in A). Topical betamethasone was not prescribed prior to FGA; (B) Panoramic FFA image showing perivasculitis (arrows), granulomas (arrowheads), and chorioretinitis (stars) mostly located in Zone III (extreme peripheral area).
Figure 2.
(A,B) Images of the right eye of Case 46, a 73-year-old female in Group III with a max IOP of 47 mmHg. Photographs of FGA (A) and panoramic FFA (B) mounted on a transparent sheet indicating different zones. (A, inset) Slit-lamp gonioscopy image showing bleeding, possibly from angle NV at the same area as that of FGA. Angle NV observed by FGA showing dot fluorescein staining (arrowhead in A) and leakage (arrows in A). Topical betamethasone was not prescribed prior to FGA; (B) Panoramic FFA image showing perivasculitis (arrows), granulomas (arrowheads), and chorioretinitis (stars) mostly located in Zone III (extreme peripheral area).
Figure 3.
(A–C) Images of the right eye of Case 54, an 18-year-old male in Group III with a max IOP of 16 mmHg; (D,E) Images of the left eye of Case 4, a 52-year-old male in Group 1 with a max IOP of 31 mmHg; (F,G) Images of the right eye of Case 3, and 22-year-old male in Group 1 with a max IOP of 18 mmHg. Gonioscopy photographs taken (A) before and (D) after the start of topical betamethasone. Granuloma was not found prior the medication being applied (A). In Case 54 (C) and Case 4 (E), angle NV (ANV) remained at 0.8 and 1.6 years, respectively, after the start of a 3- to 4-times daily continuous topical betamethasone administration. In Case 4, IOP lowered from 31 to 14 mmHg (E) and the nodules disappeared (D) after the start of topical betamethasone, yet FGA clearly demonstrated ANV (E). Changes observed after the start of the topical betamethasone in both eyes were that the circumferential parts of ANV (small black arrow heads in B) almost disappeared (C) or showed no leakage of fluorescein die (small arrowheads in E). Red, yellow, and blue arrowheads in B and C indicate the respective corresponding areas. In other cases, the circumferential areas of ANV were not visible due to being blocked by nodules (small arrowheads in F) or being obscured by the trabecular meshwork. Large white arrowheads in D and E, and F and G indicate corresponding areas, respectively. No topical steroid was prescribed at the time of FGA (G).
Figure 3.
(A–C) Images of the right eye of Case 54, an 18-year-old male in Group III with a max IOP of 16 mmHg; (D,E) Images of the left eye of Case 4, a 52-year-old male in Group 1 with a max IOP of 31 mmHg; (F,G) Images of the right eye of Case 3, and 22-year-old male in Group 1 with a max IOP of 18 mmHg. Gonioscopy photographs taken (A) before and (D) after the start of topical betamethasone. Granuloma was not found prior the medication being applied (A). In Case 54 (C) and Case 4 (E), angle NV (ANV) remained at 0.8 and 1.6 years, respectively, after the start of a 3- to 4-times daily continuous topical betamethasone administration. In Case 4, IOP lowered from 31 to 14 mmHg (E) and the nodules disappeared (D) after the start of topical betamethasone, yet FGA clearly demonstrated ANV (E). Changes observed after the start of the topical betamethasone in both eyes were that the circumferential parts of ANV (small black arrow heads in B) almost disappeared (C) or showed no leakage of fluorescein die (small arrowheads in E). Red, yellow, and blue arrowheads in B and C indicate the respective corresponding areas. In other cases, the circumferential areas of ANV were not visible due to being blocked by nodules (small arrowheads in F) or being obscured by the trabecular meshwork. Large white arrowheads in D and E, and F and G indicate corresponding areas, respectively. No topical steroid was prescribed at the time of FGA (G).
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Figure 4.
(A–D) Images of the right eye of Case 40, a 23-year-old male in Group II with a max IOP of 14 mmHg. Photographs of FFA mounted on a transparent sheet with different zones (A) and fundus (B). Photograph C and D (early stage (C) and late stage (D) of fluorescein injection) are high magnification images of the boxed area in (A). The FFA photograph in A, inset is the oval-shape encircled area shown in A taken 2.8 years after the FFA of A. Nodules in the retina completely disappeared in 2.8 years (A, inset) with no systemic steroid medication. Arrowheads in A: perivascular nodules. Postcapillary venules became dilated (arrowhead in C) and showed leakage (arrowhead in D) in the nodule adjacent to the vein (arrowhead in B).
Figure 4.
(A–D) Images of the right eye of Case 40, a 23-year-old male in Group II with a max IOP of 14 mmHg. Photographs of FFA mounted on a transparent sheet with different zones (A) and fundus (B). Photograph C and D (early stage (C) and late stage (D) of fluorescein injection) are high magnification images of the boxed area in (A). The FFA photograph in A, inset is the oval-shape encircled area shown in A taken 2.8 years after the FFA of A. Nodules in the retina completely disappeared in 2.8 years (A, inset) with no systemic steroid medication. Arrowheads in A: perivascular nodules. Postcapillary venules became dilated (arrowhead in C) and showed leakage (arrowhead in D) in the nodule adjacent to the vein (arrowhead in B).
Figure 5.
(A–D) Images of the right eye of Case 32, a 55-year-old female in Group II with a max IOP of 18 mmHg. Photographs of the fundus (A,C) and FFA (B,D). Nodule (arrowhead in A) shows almost the same size of fluorescein leakage (arrowhead in B). Nodules in the optic nerve head (C) show a granular staining pattern of fluorescein leakage (D).
Figure 5.
(A–D) Images of the right eye of Case 32, a 55-year-old female in Group II with a max IOP of 18 mmHg. Photographs of the fundus (A,C) and FFA (B,D). Nodule (arrowhead in A) shows almost the same size of fluorescein leakage (arrowhead in B). Nodules in the optic nerve head (C) show a granular staining pattern of fluorescein leakage (D).
Figure 6.
(A–C) Images of the right eye of Case 9, a 33-year-old male in Group I with a max IOP of 12 mmHg. Photographs of the fundus (A), indocyanine green angiography (B), and FFA on a mounted transparent sheet with different zones (C). Giant nodule located in the choroid (stars in A–C) showing no filling of indocyanine green (B). Fluorescein leakage can be seen at the center of the giant nodule (C).
Figure 6.
(A–C) Images of the right eye of Case 9, a 33-year-old male in Group I with a max IOP of 12 mmHg. Photographs of the fundus (A), indocyanine green angiography (B), and FFA on a mounted transparent sheet with different zones (C). Giant nodule located in the choroid (stars in A–C) showing no filling of indocyanine green (B). Fluorescein leakage can be seen at the center of the giant nodule (C).
Figure 7.
(A–C) Images of the left eye of Case 5, a 64-year-old female in Group I with a max IOP of 28 mmHg. Photographs of FFA mounted on a transparent sheet with different zones (A) and FFA in the late stage (B,C). Abnormalities of the retina existed from Zone I to III. Numerous nodules (arrowheads in A) were found mainly in Zone III. Diffuse fluorescein leakage of the optic nerve head and macular edema were found in the late stage (B). Image C is an enlargement of the boxed area in A. The retinal vein became very narrow with a long length (arrowheads in C).
Figure 7.
(A–C) Images of the left eye of Case 5, a 64-year-old female in Group I with a max IOP of 28 mmHg. Photographs of FFA mounted on a transparent sheet with different zones (A) and FFA in the late stage (B,C). Abnormalities of the retina existed from Zone I to III. Numerous nodules (arrowheads in A) were found mainly in Zone III. Diffuse fluorescein leakage of the optic nerve head and macular edema were found in the late stage (B). Image C is an enlargement of the boxed area in A. The retinal vein became very narrow with a long length (arrowheads in C).
Figure 8.
(A) Image of the right eye of Case 51, a 31-year-old male in Group III with a max IOP of 22 mmHg; (B) Image of the right eye of Case 6, a 65-year-old male in Group I with a max IOP of 28 mmHg. The FFA photographs were mounted on a transparent sheet with different zones. Flow in the retinal vein was abruptly stopped for 2–3 optic disc diameters (between the two arrowheads in A). The avascular area in B (stars) was wider than that in A (star) because of 4 branch veins (arrowheads in B) that were occluded. Retinal photocoagulation was performed in both eyes of the patients for the nonperfusion areas. Vascular occlusion (stars in A and B) occurred mainly in Zone II and III (A,B), respectively. The right eye of Case 6 had undergone trabeculectomy.
Figure 8.
(A) Image of the right eye of Case 51, a 31-year-old male in Group III with a max IOP of 22 mmHg; (B) Image of the right eye of Case 6, a 65-year-old male in Group I with a max IOP of 28 mmHg. The FFA photographs were mounted on a transparent sheet with different zones. Flow in the retinal vein was abruptly stopped for 2–3 optic disc diameters (between the two arrowheads in A). The avascular area in B (stars) was wider than that in A (star) because of 4 branch veins (arrowheads in B) that were occluded. Retinal photocoagulation was performed in both eyes of the patients for the nonperfusion areas. Vascular occlusion (stars in A and B) occurred mainly in Zone II and III (A,B), respectively. The right eye of Case 6 had undergone trabeculectomy.
Figure 9.
(A) Image of the right eye of Case 3, a 22-year-old male in Group I with a max IOP of 18 mmHg; (B) Image of the right eye of Case 12, a 22-year-old male in Group I with a max IOP of 15 mmHg; (C) Image of the right eye of Case 29, a 77-year-old male in Group II with a max IOP of 35mmHg. Photographs of FFA (A,B) and FFA mounted on a transparent sheet with different zones (C). Neovascularization (arrow in A) and occlusion of the blood vessels (arrows in B) were observed in the lattice-like degeneration (encircled area in A) and adjacent to the retinal tear (arrowhead in B and B, inset), respectively. There was local retinal detachment with fluorescein staining of pigment epithelium (B). Retinal photocoagulation was performed for the retinal tear (arrowhead in C) in the chorioretinal atrophy (star in C).
Figure 9.
(A) Image of the right eye of Case 3, a 22-year-old male in Group I with a max IOP of 18 mmHg; (B) Image of the right eye of Case 12, a 22-year-old male in Group I with a max IOP of 15 mmHg; (C) Image of the right eye of Case 29, a 77-year-old male in Group II with a max IOP of 35mmHg. Photographs of FFA (A,B) and FFA mounted on a transparent sheet with different zones (C). Neovascularization (arrow in A) and occlusion of the blood vessels (arrows in B) were observed in the lattice-like degeneration (encircled area in A) and adjacent to the retinal tear (arrowhead in B and B, inset), respectively. There was local retinal detachment with fluorescein staining of pigment epithelium (B). Retinal photocoagulation was performed for the retinal tear (arrowhead in C) in the chorioretinal atrophy (star in C).
Figure 10.
(A,B) Light microscopy photographs of the optic nerve in the right eye of Autopsy Case 1, a 75-year-old female with a max IOP of 26 mmHg (Epon embedding, toluidine blue stain). Image B is a higher magnification of the boxed area in A. The location of the optic nerve was 2 mm from the optic nerve head. The nerve fiber bundles were replaced by fibrotic tissue (stars in A). Granuloma (Gr in B) was found close to the pia mater (boxed area in A). Infiltration of lymphocytes were observed adjacent to blood vessel (arrow in B).
Figure 10.
(A,B) Light microscopy photographs of the optic nerve in the right eye of Autopsy Case 1, a 75-year-old female with a max IOP of 26 mmHg (Epon embedding, toluidine blue stain). Image B is a higher magnification of the boxed area in A. The location of the optic nerve was 2 mm from the optic nerve head. The nerve fiber bundles were replaced by fibrotic tissue (stars in A). Granuloma (Gr in B) was found close to the pia mater (boxed area in A). Infiltration of lymphocytes were observed adjacent to blood vessel (arrow in B).
Figure 11.
Light microscopy photographs of the peripheral area of the retina and choroid in the right eye of Autopsy Case 2, a 78-year-old female with a max IOP of 22 mmHg (methylmethacrylate embedding, toluidine blue stain). The retina and choroid became very thin (small star) at the center of chorioretinal atrophy, which was surrounded by abnormally thick fibrotic tissue in the choroid (large stars).
Figure 11.
Light microscopy photographs of the peripheral area of the retina and choroid in the right eye of Autopsy Case 2, a 78-year-old female with a max IOP of 22 mmHg (methylmethacrylate embedding, toluidine blue stain). The retina and choroid became very thin (small star) at the center of chorioretinal atrophy, which was surrounded by abnormally thick fibrotic tissue in the choroid (large stars).
Figure 12.
(A–C) Light microscopy photograph of granuloma (Gr) adjacent to the retinal artery (A) located in the area of radial peripapillary capillaries, and transmission electron microscopy photographs (B,C) in the left eye of Autopsy Case 1, 75-year-old female. B and C are ultrathin sections of granuloma (Gr) and boxed area in (A), respectively. Epon embedding, toluidine blue stain. Granulomas were composed of macrophages (MP in B) and had subplasmalemmal linear density (arrowheads in B, inset). The inset in (B) is a high magnification of the boxed area in B. The arterial wall became thick because of basal lamina layering (stars in C). Lymphocytes (Ly in C) were observed under the endothelium of the artery.
Figure 12.
(A–C) Light microscopy photograph of granuloma (Gr) adjacent to the retinal artery (A) located in the area of radial peripapillary capillaries, and transmission electron microscopy photographs (B,C) in the left eye of Autopsy Case 1, 75-year-old female. B and C are ultrathin sections of granuloma (Gr) and boxed area in (A), respectively. Epon embedding, toluidine blue stain. Granulomas were composed of macrophages (MP in B) and had subplasmalemmal linear density (arrowheads in B, inset). The inset in (B) is a high magnification of the boxed area in B. The arterial wall became thick because of basal lamina layering (stars in C). Lymphocytes (Ly in C) were observed under the endothelium of the artery.
Figure 13.
(A–C) Light microscopy photographs of retinal vein in ordinal (A,C) and tangential sections (B) of the left eye of Autopsy Case 1, a 75-year-old female. (A,B) Methylmethacrylate embedding, toluidine blue stain. (C) Paraffin embedding, PAM stain. Granuloma (Gr in A and B) accompanying lymphocytes seemed to push the vein wall. The basement membrane seemed to be very thick (arrowheads in A–C). The blood vessel in the retina was occluded (C).
Figure 13.
(A–C) Light microscopy photographs of retinal vein in ordinal (A,C) and tangential sections (B) of the left eye of Autopsy Case 1, a 75-year-old female. (A,B) Methylmethacrylate embedding, toluidine blue stain. (C) Paraffin embedding, PAM stain. Granuloma (Gr in A and B) accompanying lymphocytes seemed to push the vein wall. The basement membrane seemed to be very thick (arrowheads in A–C). The blood vessel in the retina was occluded (C).
Figure 14.
(A–C) Transmission electron microscopy photographs of retinal blood vessels in tangential sections (A–C) of the left eye of Autopsy Case 1, a 75-year-old female. Samples of the retina were taken from the area of the radial peripapillary capillaries (A,B; large magnification of the area pointed by arrow in A) and the periphery (C). Macrophage (MP) surrounding the postcapillary venule (PCV) and endothelium of the PCV was infiltrated by inflammatory cells (arrowhead in B). The endothelium of the retinal blood vessel had many vacuoles (inset in C) along the junctional areas (arrowheads in C). Some of the vacuoles contained fibrillar materials (arrow in C, inset). Ly: lymphocytes, Mn: monocytes, V: retinal vein.
Figure 14.
(A–C) Transmission electron microscopy photographs of retinal blood vessels in tangential sections (A–C) of the left eye of Autopsy Case 1, a 75-year-old female. Samples of the retina were taken from the area of the radial peripapillary capillaries (A,B; large magnification of the area pointed by arrow in A) and the periphery (C). Macrophage (MP) surrounding the postcapillary venule (PCV) and endothelium of the PCV was infiltrated by inflammatory cells (arrowhead in B). The endothelium of the retinal blood vessel had many vacuoles (inset in C) along the junctional areas (arrowheads in C). Some of the vacuoles contained fibrillar materials (arrow in C, inset). Ly: lymphocytes, Mn: monocytes, V: retinal vein.
Figure 15.
(A) Light microscopy photograph granuloma (Gr) in the retina taken from the transitional area from radial peripapillary capillaries to the mid periphery in the right eye of Autopsy Case 2, a 78-year-old female (methylmethacryrate embedding, toluidine blue stain); (B) Scanning electron microscopy photographs of granuloma extending from the retina to the vitreous in the right eye of Autopsy Case 1, a 75-year-old female; (C) Transmission electron microscopy of granuloma in the left eye of Autopsy Case 1; (D,E) Light microscopy photographs of the retina in the mid periphery (D) and extremely periphery (E) in the left eye of Autopsy Case 1. Hematoxylin & eosin stain, paraffin embedding; (F) Light microscopy photograph of snowball vitreous opacity obtained from a vitrectomy sample. Epon embedding, toluidine blue stain. Macrophages (arrowheads in A, C and MP in B, C) invading from retina into the vitreous (V). Proliferative tissue (arrowheads in D) consisting of fibrotic tissue with lymphocytic infiltration adjacent to the retinal vein (arrow in D) extending from the retina to the vitreous. Vitreoretinal adhesion where the retina became degenerated (star in E) was observed in the extreme peripheral area. The snowball (SB in F) opacity is granuloma. FFA showed diffuse and strong leakage from blood vessels (figure not shown).
Figure 15.
(A) Light microscopy photograph granuloma (Gr) in the retina taken from the transitional area from radial peripapillary capillaries to the mid periphery in the right eye of Autopsy Case 2, a 78-year-old female (methylmethacryrate embedding, toluidine blue stain); (B) Scanning electron microscopy photographs of granuloma extending from the retina to the vitreous in the right eye of Autopsy Case 1, a 75-year-old female; (C) Transmission electron microscopy of granuloma in the left eye of Autopsy Case 1; (D,E) Light microscopy photographs of the retina in the mid periphery (D) and extremely periphery (E) in the left eye of Autopsy Case 1. Hematoxylin & eosin stain, paraffin embedding; (F) Light microscopy photograph of snowball vitreous opacity obtained from a vitrectomy sample. Epon embedding, toluidine blue stain. Macrophages (arrowheads in A, C and MP in B, C) invading from retina into the vitreous (V). Proliferative tissue (arrowheads in D) consisting of fibrotic tissue with lymphocytic infiltration adjacent to the retinal vein (arrow in D) extending from the retina to the vitreous. Vitreoretinal adhesion where the retina became degenerated (star in E) was observed in the extreme peripheral area. The snowball (SB in F) opacity is granuloma. FFA showed diffuse and strong leakage from blood vessels (figure not shown).
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Figure 16.
(A–F). Light microscopy photographs of the angle in trabeculectomy (TRAB) specimens. (A–F) immunohistochemical staining of CD68. (A–F inset) Hematoxylin eosin stain of paraffin embedding. (A) Image of the right eye in Case 24, a 39-year-old female in Group I with a max IOP of 34 mmHg; (B) Image of the right eye in Case 21, a 72-year-old female in Group I with a max IOP of 32 mmHg; (C) Image of the left eye in Case 23, a 72-year-old male in Group I with a max IOP of 35 mmHg; (D) Image of the left eye in Case 20, a 72-year-old male in Group I with a max IOP of 50 mmHg; (E,F) Image of the left eye in Case 44, a 74-year-old male in Group III with a max IOP of 54 mmHg. Scale bar: 50 μm. Granuloma (Gr) was found in the pupil area, around the collector channel (CC, open arrowhead in B), in the Schlemm’s canal (SC, solid arrow-heads in B and C), and the iris root (Gr in D, arrowhead in D inset). CD68-positive cells were not found with a continuous topical betamethasone (CTB) in the first TRAB (E), but were found around the SC, collector channel (CC), and in the trabecular meshwork in the second TRAB. This eye was a dilemma case of super mild steroid responder. When CTB (4 to 6 times daily) was continued for 7 months, IOP temporally decreased from 36 mmHg to 15 mmHg. However, it started to increase to 23 mmHg, so CTB was discontinued for 1 week and IOP increased again to 34 mmHg. The second TRAB was then performed in 4 days after the restart of the topical betamethasone. CD-positive cells and lymphocytes infiltration still remained in the SC and the CCs; (G) Light microscopy photographs of the angle obtained from TRAB in the right eye of Case 27, a 33-year-old female in Group II with a max IOP of 38 mmHg (thrombomodulin immunohistochemical stain). The inset is a lower magnification image of photo G (Masson trichrome stain). CM: ciliary muscle, I: iris, arrowhead in inset: peripheral anterior synechia (PAS). Scale bar: 50 μm. The patient was referred to our hospital in December 1991 due to BHL. Perivascular nodules in the retina and slight inflammation in the anterior chamber were found. IOP had remained at 12–14 mmHg in both eyes for 18 years. IOP in her right eye started to increase to 20 mmHg from March 2009, and topical betamethasone was then started. However, the patient administered the medication irregularly. PAS with 50% (arrowhead in G, inset) occurred at 21 months of absence from our hospital. IOP in her right eye increased to 38 mmHg and VFD worsened from normal (March 2011) to Stage V (January 2016) in A-G classification. Because of no response to IOP (i.e., IOP fluctuated around 30 mmHg) by topical betamethasone and glaucoma medication, TRAB combined with tube-shunt surgery was performed in October 2016. Only a small part of Schlemm’s canal (SC) remained open (open arrowheads) and the center part of SC became occluded (solid arrowheads). There was infiltration of melanocytes on the surface of trabecular meshwork (arrows in G). No inflammation in the anterior chamber and no elevation of IOP was observed with continuous topical betamethasone administered 3-times daily for 4-years postoperative; (H,I) Light microscopy photographs of the angle at the 9-o’clock position in the left eye of Autopsy Case 1 (H), a 75-year-old female, and at the 9-o’clock position in the left eye of Autopsy Case 2 (I), a 78-year-old female. The inset in I is a high magnification image of the granuloma (arrowhead in I). Methylmethacrylate embedding, toluidine blue stain. Granulomas (Gr in H, arrowhead in I) were found in the Schlemm’s canal (SC). The SC is almost occluded in photos H and I. The granuloma composed of epithelioid cells appeared to be shrinking and disappearing (I inset). Scale bar in F, G: 50 μm.
Figure 16.
(A–F). Light microscopy photographs of the angle in trabeculectomy (TRAB) specimens. (A–F) immunohistochemical staining of CD68. (A–F inset) Hematoxylin eosin stain of paraffin embedding. (A) Image of the right eye in Case 24, a 39-year-old female in Group I with a max IOP of 34 mmHg; (B) Image of the right eye in Case 21, a 72-year-old female in Group I with a max IOP of 32 mmHg; (C) Image of the left eye in Case 23, a 72-year-old male in Group I with a max IOP of 35 mmHg; (D) Image of the left eye in Case 20, a 72-year-old male in Group I with a max IOP of 50 mmHg; (E,F) Image of the left eye in Case 44, a 74-year-old male in Group III with a max IOP of 54 mmHg. Scale bar: 50 μm. Granuloma (Gr) was found in the pupil area, around the collector channel (CC, open arrowhead in B), in the Schlemm’s canal (SC, solid arrow-heads in B and C), and the iris root (Gr in D, arrowhead in D inset). CD68-positive cells were not found with a continuous topical betamethasone (CTB) in the first TRAB (E), but were found around the SC, collector channel (CC), and in the trabecular meshwork in the second TRAB. This eye was a dilemma case of super mild steroid responder. When CTB (4 to 6 times daily) was continued for 7 months, IOP temporally decreased from 36 mmHg to 15 mmHg. However, it started to increase to 23 mmHg, so CTB was discontinued for 1 week and IOP increased again to 34 mmHg. The second TRAB was then performed in 4 days after the restart of the topical betamethasone. CD-positive cells and lymphocytes infiltration still remained in the SC and the CCs; (G) Light microscopy photographs of the angle obtained from TRAB in the right eye of Case 27, a 33-year-old female in Group II with a max IOP of 38 mmHg (thrombomodulin immunohistochemical stain). The inset is a lower magnification image of photo G (Masson trichrome stain). CM: ciliary muscle, I: iris, arrowhead in inset: peripheral anterior synechia (PAS). Scale bar: 50 μm. The patient was referred to our hospital in December 1991 due to BHL. Perivascular nodules in the retina and slight inflammation in the anterior chamber were found. IOP had remained at 12–14 mmHg in both eyes for 18 years. IOP in her right eye started to increase to 20 mmHg from March 2009, and topical betamethasone was then started. However, the patient administered the medication irregularly. PAS with 50% (arrowhead in G, inset) occurred at 21 months of absence from our hospital. IOP in her right eye increased to 38 mmHg and VFD worsened from normal (March 2011) to Stage V (January 2016) in A-G classification. Because of no response to IOP (i.e., IOP fluctuated around 30 mmHg) by topical betamethasone and glaucoma medication, TRAB combined with tube-shunt surgery was performed in October 2016. Only a small part of Schlemm’s canal (SC) remained open (open arrowheads) and the center part of SC became occluded (solid arrowheads). There was infiltration of melanocytes on the surface of trabecular meshwork (arrows in G). No inflammation in the anterior chamber and no elevation of IOP was observed with continuous topical betamethasone administered 3-times daily for 4-years postoperative; (H,I) Light microscopy photographs of the angle at the 9-o’clock position in the left eye of Autopsy Case 1 (H), a 75-year-old female, and at the 9-o’clock position in the left eye of Autopsy Case 2 (I), a 78-year-old female. The inset in I is a high magnification image of the granuloma (arrowhead in I). Methylmethacrylate embedding, toluidine blue stain. Granulomas (Gr in H, arrowhead in I) were found in the Schlemm’s canal (SC). The SC is almost occluded in photos H and I. The granuloma composed of epithelioid cells appeared to be shrinking and disappearing (I inset). Scale bar in F, G: 50 μm.
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Table 1.
(A) Patients in the clinical and pathological studies (n = 57 patients); (B) Patients in the pathological study.
Table 1.
(A) Patients in the clinical and pathological studies (n = 57 patients); (B) Patients in the pathological study.
(A) |
Age | Gender | Mean Observation Period (Years) | BCVA |
52.6 ± 19.03 | female (54%) | 8.78 ± 7.52 | −0.34 ± 0.74 |
BCVA: best-corrected visual acuity in logMAR. |
(B) |
Type of Specimens | Age | Gender | Max IOP (R/L, mmHg) |
TRAB (14 eyes) *1 | 61.29 ± 17.14 | M: 7, F: 7 | 42.64 ± 10.43 *2 |
Autopsy Case 1 | 75 | F | 26/24 |
Autopsy Case 2 | 78 | F | 22/23 |
Autopsy Case 3 | 44 | F | 14/10 |
Autopsy Case 4 | 90 | M | / |
Autopsy Case 5 | 67 | F | / |
Biopsy Case 6 *3 | 32 | F | 38 *2 |
Table 2.
Patient age, gender, and observation periods in each Group of the clinical study (I: biopsy proven, II: bilateral hilar lymphadenopathy (BHL) positive, III: BHL negative).
Table 2.
Patient age, gender, and observation periods in each Group of the clinical study (I: biopsy proven, II: bilateral hilar lymphadenopathy (BHL) positive, III: BHL negative).
Group (n) | Mean Patient Age (Years) | Gender | Mean Observation Period (Years) |
---|
Group I (24) | 53.92 ± 18.88 | F = 13, M = 11 | 9.21 ± 6.23 |
Group II (19) | 48.47 ± 16.88 | F = 11, M = 8 | 8.91 ± 9.13 |
Group III (14) | 55.93 ± 22.23 | F = 7, M = 7 | 7.86 ± 7.62 |
p-value | 0.496 *1 | 0.9433 *2 | 0.867 *1 |
Table 3.
Best-corrected visual acuity (BCVA), max intraocular pressure (Max IOP) and visual field defect (Aulhorn-Greve classification) in each Group.
Table 3.
Best-corrected visual acuity (BCVA), max intraocular pressure (Max IOP) and visual field defect (Aulhorn-Greve classification) in each Group.
Group (n) | BCVA | Max IOP (mmHg) | A-G |
---|
Group I (24) | −0.33 ± 0.74 | 30.13 ± 13.67 | 1.71 |
Group II (19) | −0.56 ± 0.74 | 27.21 ± 10.61 | 1.17 (18) * |
Group III (14) | −0.07 ± 0.72 | 33.64 ± 15.14 | 2.57 |
p-value | 0.179 | 0.386 | 0.202 |
Table 4.
Correlation of the max IOP (mmHg) with anterior segment manifestations and vitreous findings at the presentation.
Table 4.
Correlation of the max IOP (mmHg) with anterior segment manifestations and vitreous findings at the presentation.
| KP (n) | Nodule in the Angle (n) | PAS (n) | Vitreous (n) |
---|
Positive | 32.70 (30) | 31.50 (44) | 30.97 (35) | 31.63 (16) |
Negative | 27.04 (27) | 25.00 (13) | 28.50 (22) | 29.39 (41) |
p-value | 0.1005 | 0.02696 | 0.5183 | 0.5311 |
Table 5.
(A) Logistic regression analysis of VFD in Aulhorn-Greve (A–G) among the different parameters (i.e., patient age, gender, number of manifestations in the three different zones, KPs, nodule in the angle, and snowball opacity) as evaluated by the Hosmer-Lemeshow test; (B) Logistic regression analysis of glaucoma surgery among the different parameters (i.e., patient age, gender, number of manifestations in the three different zones, KPs, nodule in the angle, and snowball opacity) as evaluated by the Hosmer-Lemeshow test.
Table 5.
(A) Logistic regression analysis of VFD in Aulhorn-Greve (A–G) among the different parameters (i.e., patient age, gender, number of manifestations in the three different zones, KPs, nodule in the angle, and snowball opacity) as evaluated by the Hosmer-Lemeshow test; (B) Logistic regression analysis of glaucoma surgery among the different parameters (i.e., patient age, gender, number of manifestations in the three different zones, KPs, nodule in the angle, and snowball opacity) as evaluated by the Hosmer-Lemeshow test.
(A) |
Expl Var | CE | p-Value |
Intercept | −6.19 | 0.0982 |
Age | −0.05 | 0.3403 |
Gender | 2.13 | 0.2164 |
Zone I | −0.03 | 0.9609 |
Zone II | −1.35 | 0.2712 |
Zone III | −0.92 | 0.3348 |
Max IOP | 0.35 | 0.0151 |
KP | −0.72 | 0.6159 |
Nodule * | 0.00 | 0.9982 |
SB | 1.05 | 0.5370 |
(B) |
Expl Var | CE | p-Value |
Intercept | −6.19 | 0.0982 |
Age | −0.05 | 0.3403 |
Gender | 2.13 | 0.2164 |
Zone I | −0.01 | 0.9887 |
Zone II | −1.98 | 0.0611 |
Zone III | 1.96 | 0.0484 |
Max IOP | 0.12 | 0.1330 |
A-G | 0.99 | 0.0349 |
KP | 0.31 | 0.8125 |
Nodule * | −2.30 | 0.3752 |
SB | 1.07 | 0.5104 |