Lacrimal Gland and Orbital Lesions in LatY136F Knock-in Mice, a Model for Human IgG4-Related Ophthalmic Disease.

PURPOSE: LatY136F knock-in mice were recently proposed as an animal model for immunoglobulin G4 (IgG4)-related disease. In this study, we investigated whether LatY136F knock-in mice exhibit ophthalmic lesions, specifically in the lacrimal and Harderian glands. METHODS: Lacrimal glands, Harderian glands, and adherent lymphoid follicle lesions were dissected from LatY136F knock-in mice and wild type (WT) C57BL/6 mice between 6 and 24 weeks of age. Tissues were stained with hematoxylin-eosin, immunoglobulin G (IgG), and anti-IgG1, a homologue of human IgG4, for histopathological analysis. RESULTS: In LatY136F knock-in mice, IgG1-positive cells infiltrated the space between the lacrimal gland acinar cells at 6, 9, 12, and 20 weeks or order, and the number of IgG1-positive cells did not differ significantly between these age groups. Infiltration of IgG1-positive inflammatory cell was also observed in the Harderian glands of LatY136F knock-in mice at all ages. The ratio of IgG1/IgG-positive cells averaged 80 and 67% in the lacrimal and Harderian glands, respectively. Dense IgG1-positive lesions were also seen in tissues adjacent to the lacrimal and Harderian glands in some LatY136F knock-in mice. In contrast, there were almost no IgG1-positive cell infiltrates in the lacrimal and Harderian glands of WT mice. CONCLUSION: IgG1-positive cells infiltrate the lacrimal and Harderian glands of LatY136F knock-in mice, indicating that LatY136F knock-in mice could be a representative animal model for IgG4-related ophthalmic disease.

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

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

Combined Keratoplasty, Pars Plana Vitrectomy, and Flanged Intrascleral Intraocular Lens Fixation to Restore Vision in Complex Eyes With Coexisting Anterior and Posterior Segment Problems.

PURPOSE: To restore vision in complex eyes with coexisting anterior and posterior segment problems, combined corneal transplantation (penetrating keratoplasty [PK] or Descemet-stripping automated endothelial keratoplasty [DSAEK]), pars plana vitrectomy (PPV), and/or flanged intrascleral intraocular lens (IOL) fixation, designated vitreocorneal surgery are performed. In this study, we evaluated the usefulness of vitreocorneal surgery for eyes with complex comorbidities. METHODS: Thirteen consecutive eyes in 13 patients with coexisting corneal pathology (ie, corneal scarring, bullous keratoplasty, corneal laceration) and posterior segment pathology (ie, aphakia without capsular support, retinal detachment, intravitreal foreign body) underwent vitreocorneal surgery. Visual outcomes, intraoperative and postoperative complications, and additional surgery were retrospectively evaluated. RESULTS: Vitreocorneal surgery included PK + PPV + intrascleral IOL fixation (n = 5), PK + PPV (n = 3), PK + intrascleral IOL fixation (n = 1), DSAEK + intrascleral IOL fixation (n = 1), and DSAEK + PPV + intrascleral IOL fixation (n = 3). An intraoperative Eckardt temporary keratoprosthesis use enabled safe PPV. No vitreoretinal/IOL complications occurred. One eye required repeat DSAEK to repair endothelial graft detachment and inversion. In 3 eyes, secondary glaucoma was subsequently treated by glaucoma drainage device implantation through the pars plana. Mean best spectacle-corrected visual acuity (logMAR) improved from 1.8 ± 0.9 preoperatively to 1.1 ± 0.6 at 11.2 ± 14.6 months postoperatively (P = 0.002). Postoperative refraction was -0.68 ± 2.56 D (spherical equivalent). CONCLUSIONS: PK or DSAEK with PPV and/or flanged intrascleral IOL fixation is useful for complex eyes with coexisting anterior and posterior segment problems.

METAMORPHOPSIA AND OUTER RETINAL MORPHOLOGIC CHANGES AFTER SUCCESSFUL VITRECTOMY SURGERY FOR MACULA-OFF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate the correlation between metamorphopsia and outer retinal morphologic changes after successful vitrectomy for rhegmatogenous retinal detachment (RRD). METHODS: Forty eyes from 40 patients with macula-off (26 eyes) or macula-on (14 eyes) RRDs that underwent pars plana vitrectomy were included. Metamorphopsia was quantified with M-CHARTS. The relationship between the integrity of the outer retinal layers examined by spectral domain optical coherence tomography and metamorphopsia at 6 and 12 months postoperatively was evaluated. RESULTS: Metamorphopsia was significantly more frequent in eyes with macula-off RRD (88%) than in eyes with macula-on RRD (21%) at 6 months postoperatively (P < 0.001) and became significantly less frequent in macula-off RRD eyes from 6 months to 12 months (64%) postoperatively (P = 0.041). Horizontal metamorphopsia scores in eyes with continuous interdigitation zone and ellipsoid zone bands were significantly smaller than in eyes with a disrupted interdigitation zone band and a continuous ellipsoid zone band or in eyes with disrupted ellipsoid zone and interdigitation zone bands (P = 0.003 and P <0.001, respectively), which was consistent with the results of vertical metamorphopsia scores. CONCLUSION: Restoration of both the ellipsoid zone and interdigitation zone bands seems to be an important factor for the reduction of metamorphopsia after successful vitrectomy for macula-off RRD.

MACULAR HOLE CLOSURE OVER RESIDUAL SUBRETINAL FLUID BY AN INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE IN PATIENTS WITH MACULAR HOLE RETINAL DETACHMENT IN HIGH MYOPIA.

PURPOSE: To describe the closure of a macular hole over residual subretinal fluid in patients with macular hole retinal detachment in high myopia who had been treated using an inverted internal limiting membrane flap technique. METHODS: Three patients with macular hole retinal detachment in high myopia underwent pars plana vitrectomy using the inverted internal limiting membrane flap technique. One patient received a silicone oil injection, and the other two patients received a long-acting gas injection at the end of the surgery. After surgery, spectral domain ocular coherence tomography examination was performed. RESULTS: In the patient with the silicone oil injection, spectral domain optical coherence tomography revealed that the macular hole was sealed with an inverted internal limiting membrane flap in the presence of subretinal fluid 1 day after surgery. The inner retinal layers gradually regained a more physiologic configuration over the residual subretinal fluid. In all patients, macular holes were completely closed over the subretinal fluid, which was gradually absorbed. CONCLUSION: Using the inverted internal limiting membrane flap technique, macular holes were closed over residual subretinal fluid in patients with macular hole retinal detachment. The results indicate that reattachment of the retina may not be necessary for closure of macular holes.

Paclitaxel-Releasing Thin Biodegradable Film for Prevention of Bleb Avascularity Without Compromising Filtration in Rabbits.

PURPOSE: A honeycomb-patterned film (HPF) prevents bleb scarring and mitomycin C (MMC)-related bleb avascularity in a rabbit model of filtration surgery. In this study, we examined whether a HPF-releasing paclitaxel (PTX) can prevent bleb avascularity without compromising filtration. METHODS: Filtration surgery was performed in one eye of rabbits. A 14-µm thick HPF made from poly(L-lactide-co-ε-caprolactone) was placed subconjunctivally over the filtration site with the honeycomb surface turned toward the subconjunctival Tenon tissue. The rabbits were divided into four groups (n = 5 each): 1, HPF with no drug; 2, HPF + PTX 50 µg; 3, HPF + 5 µg; 4, HPF + 0.5 µg. Intraocular pressure (IOP) measurements and bleb evaluations using ultrasound biomicroscopy were performed periodically for 4 weeks followed by histological examination. A longer follow-up study (12 weeks) was performed for group 4 (experiment 2; n = 8). RESULTS: Among all groups at the 4-week follow up, two blebs failed in group 1. The postoperative IOP decrease was significantly greater in PTX-treated eyes than in group 1. The bleb avascular area persisted for 4 weeks in groups 2 and 3. However, no avascular area was observed in groups 1 and 4 at 4 weeks postoperatively. Histology showed minimal fibrosis at the filtration site in all the PTX groups. In experiment 2, some blebs became flatter starting at 10 weeks after surgery. CONCLUSIONS: PTX released from HPF promoted bleb survival and IOP decrease. The lowest dose of PTX (0.5 µg) was effective at preventing bleb avascularity without compromising filtration.

Subfoveal choroidal thickness change following segmental scleral buckling for rhegmatogenous retinal detachment.

PURPOSE: To report the morphologic changes of the subfoveal choroidal thickness using spectral-domain optical coherence tomography following segmental scleral buckling. DESIGN: Retrospective, observational case series. METHODS: The study included 21 eyes of 20 patients who underwent segmental scleral buckling for the treatment of rhegmatogenous retinal detachment. All patients underwent the measurements of the subfoveal choroidal thickness preoperatively and 1 week, 1 month, and 3 months after the surgery. The changes in choroidal thickness, 4 mm from the fovea, before and 1 week after surgery were analyzed in the buckled and unbuckled side. RESULTS: The preoperative mean subfoveal choroidal thickness of operated eyes was 239.2 ± 91.0 µm. The postoperative mean subfoveal choroidal thicknesses of operated eyes at 1 week, 1 month, and 3 months were 267.6 ± 96.8 µm, 250.6 ± 95.8 µm, and 239.4 ± 95.6 µm, respectively. There were significant differences between preoperative subfoveal choroidal thickness and 1-week-postoperative and 1-month-postoperative subfoveal choroidal thicknesses (P < .01, P = .03, ANOVA), and there was no significant difference between subfoveal choroidal thicknesses preoperatively and 3 months postoperatively (P > .99, ANOVA). The changes in choroidal thickness of the buckled and unbuckled side preoperatively and 1 week postoperatively were not significantly different (n = 8, P = .589, 2-way ANOVA). CONCLUSION: The subfoveal choroidal thickness may change temporarily following segmental scleral buckling surgery. This may be the result of reversible subclinical microcirculatory dysfunction of the choroid.

Suppression of avascular bleb formation by a thin biodegradable film in a rabbit filtration surgery with mitomycin C.

BACKGROUND: Avascularity of the bleb is regarded as a risk of bleb infection, which is the most serious complication after filtration surgery with mitomycin C (MMC). There is no perfect way to prevent avascular bleb formation. We hypothesized that keeping the conjunctiva away from direct exposure to aqueous filtration may suppress avascular bleb formation after filtration surgery with MMC. In order to prove our hypothesis, we investigated whether a thin biodegradable, honeycomb-patterned film (HPF) can reduce bleb avascularity in a rabbit model of filtration surgery with mitomycin C (MMC). METHODS: A fornix-based full-thickness filtration surgery was performed in one eye of each of five rabbits (control group). The same surgery with intraoperative MMC treatment was done in both eyes of six rabbits, with one eye receiving a 14-µm-thick HPF made from poly(L-lactide-co-ε-caprolactone), which was placed subconjunctivally over the filtration site with the honeycomb surface facing up. Intraocular pressure (IOP) measurements, bleb evaluations using ultrasound biomicroscopy (UBM), and in vivo confocal microscopy (IVCM) were performed periodically for 4 weeks postoperatively followed by histological examination. RESULTS: The postoperative IOP decrease and bleb survival were significantly greater in MMC-treated eyes than in control eyes, and were similar between MMC-only and MMC + HPF eyes. The avascular area in the bleb persisted for 4 weeks in MMC-only eyes. Postoperative IVCM showed morphological changes of the conjunctival epithelial cells (i.e., enlarged and variable in size and shape) and epithelial defects in MMC-only eyes, and significantly lower density of connective tissue and vascularity in the subepithelial space in MMC-only eyes compared to the control eyes. These IVCM findings agreed with those by UBM and histology. Bleb avascularity shown by clinical bleb appearance, IVCM and histology, conjunctival epithelial damage shown by IVCM and histology, and loose subepithelial connective tissue shown by UBM, IVCM, and histology were all reduced in MMC + HPF eyes compared to MMC-only eyes. CONCLUSIONS: IVCM successfully showed the characteristic conjunctival damage in MMC-treated blebs. The concomitant use of a thin biodegradable HPF reduced avascularity and conjunctival damage in blebs, without compromising filtration in rabbits following filtration surgery with MMC.

Fundus autofluorescence and spectral-domain optical coherence tomography findings of leopard spots in nanophthalmic uveal effusion syndrome.

PURPOSE: To describe fundus autofluorescence (FAF) imaging and spectral domain optical coherence tomography (SD-OCT) findings of leopard spots in nanophthalmic uveal effusion syndrome. METHODS: A 34-year-old man with retinal detachment associated with nanophthalmic uveal effusion syndrome in the right eye underwent sclerotomy three times. After the final surgery, the subretinal fluid resolved gradually. Then, SD-OCT examination, FAF photography, fluorescein angiography (FA), and indocyanine green angiography (ICGA) were performed simultaneously with the spectralis Heidelberg retina angiograph + OCT system. RESULTS: SD-OCT revealed focal thickening of the retinal pigment epithelium (RPE) layer at the same locations as leopard spots, which appeared hypofluorescent on FA and ICGA. These spots showed hyperautofluorescence on FAF imaging. Six months later, focal thickening of the RPE layer became smaller on OCT and hyperautofluorescence was attenuated on FAF imaging. CONCLUSIONS: Simultaneous imaging of the fundus with multiple modalities including OCT, FAF, FA, and ICGA indicates that leopard spots in the fundus of uveal effusion syndrome may show hyperautofluorescence and correspond to focal thickening of the RPE layer by SD-OCT. This imaging method may help elucidate the pathology of various fundus lesions in vivo.

A thin honeycomb-patterned film as an adhesion barrier in an animal model of glaucoma filtration surgery.

PURPOSE: To evaluate the effectiveness and safety of a thin honeycomb-patterned biodegradable film for glaucoma filtration surgery in rabbits. METHODS: A 7 microm-thick film made from poly(L-lactide-co-epsilon-caprolactone) was placed in the subconjunctival space in one eye of rabbits, with or without full thickness filtration surgery. The film had a honeycomb-patterned surface that faced the subconjunctival Tenon tissue and the other side was smooth. Filtration surgery was also performed in the fellow eye, which received either no adjunctive treatment or 0.4 mg/mL mitomycin C (MMC; n=6 each). Intraocular pressure (IOP) measurements and bleb evaluations using ultrasound biomicroscopy were performed periodically for 28 days after surgery followed by histologic observation. RESULTS: Postoperative IOPs of the film-treated eyes were significantly lower than that of control eyes from day 10 to day 28 (P<0.05), but were not significantly different from those of MMC-treated eyes. The subconjunctival filtration space, detected by ultrasound biomicroscopy, disappeared in 5 control eyes, 1 MMC-treated eye, but none of the film-treated eyes. A bleb leak occurred postoperatively in 2 MMC-treated eyes. Histologically, in eyes without filtration surgery, fibrotic tissue with the film partly attached to it was noted on the honeycomb side, but was minimal on the sclera that faced the smooth side of the film. In eyes with filtration surgery, the honeycomb-patterned film lined the inner bleb wall with minimal inflammatory reaction. CONCLUSIONS: The thin honeycomb-patterned film that attached to the inner bleb wall worked as an adhesion barrier in glaucoma filtration surgery in rabbits, which is worthy of further investigation.

Postoperative retinal break after 25-gauge transconjunctival sutureless vitrectomy: report of four cases.

BACKGROUND: A 25-gauge transconjunctival sutureless vitrectomy (TSV) has been reported effective. However, complications such as postoperative retinal detachment have been reported. In this study, we report four cases of retinal breaks found after 25-gauge TSV. In this study, we investigated factors contributing to occurrence of postoperative complications. METHODS: Seventy-five patients (75 eyes) underwent 25-gauge TSV surgery at Kanazawa University hospital between April 2004 and September 2005. Postoperative follow-up monitoring was done for at least 3 months. The surgical charts were reviewed. RESULTS: Retinal breaks not accompanied by retinal detachment were noted postoperatively in four patients. All four of these patients had preoperative idiopathic macular holes. In all cases, there was no vitreous traction around the retinal break and photo coagulation was performed. One eye with age-related macular degeneration developed intraoperative rhegmatogenous retinal detachment. No other complications were observed during the intraoperative and postoperative periods. CONCLUSION: Upon performing 25-gauge TSV for macular hole repair, care should be taken to detect retinal breaks and retinal detachment intraoperatively and postoperatively.