Ten-year epidemiological study of ocular and orbital tumors in Chiba University Hospital.

BACKGROUND: The purpose of this study is to determine the epidemiology of tumors of the ocular adnexa and orbit in Japan. METHODS: We conducted a retrospective study on the histopathological reports in the medical records of the Chiba University Hospital from April 2009 to March 2019. Three hundred and seventy two records were examined. In addition, we examined the annual changes in the major types of tumors including malignant lymphomas and IgG4-related diseases (IgG4-RDs). RESULTS: There were 270 conjunctival or eyelid tumors with 166 benign and 104 malignant. There were 102 orbital tumors with 55 benign, 47 malignant tumors, and 21 cases of IgG4-RDs. Ten cases of adenoma (2.7%), another benign tumor, was also diagnosed. The major malignant tumors were malignant lymphoma in 74 cases, sebaceous gland carcinoma (SGC) in 28 cases, basal cell carcinoma in 15 cases, and squamous cell carcinoma in 8 cases. The SGCs were the most common malignant eyelid tumor at 54%. Among the malignant lymphomas, extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue type, MALT lymphomas, was the most common at 51 cases and the second most common was the diffuse large B-cell lymphoma at 11 cases. The ratio of MALT lymphomas to that of all malignant lymphomas increased significantly with years. The serum IgG4 values were measured more often in the last 5 years (70%) than in the former 5 years (33%). CONCLUSIONS: We conclude that malignant lymphoma is a major malignant tumor in Japan and pathological biopsies should be done proactively to prevent missing IgG4-positive MALT lymphomas.

Case of Macular Hole Secondary to Ocular Toxoplasmosis Treated Successfully by Vitrectomy with Inverted Internal Limiting Membrane Flap.

We report a case of ocular toxoplasmosis that developed a full-thickness macular hole (FTMH) which was successfully treated by pars plana vitrectomy combined with an inverted internal limiting membrane (ILM) flap. A 49-years-old Japanese man was aware of blurred vision in his right eye. Slit-lamp biomicroscopy, ophthalmoscopy, and optical coherence tomography (OCT) of the right eye showed that there was a grayish-white subretinal lesion at the macula accompanied by retinal exudation and mild vitreous flare and iritis. An increase in the level of serum IgM for toxoplasma led to a diagnosis of ocular toxoplasmosis. He developed a FTMH adjacent to the lesion 2 weeks after administering sulfamethoxazole/trimethoprim, and his decimal visual acuity was 0.15. Because the FTMH remained 3 months after the resolution of inflammation and his metamorphopsia persisted, vitrectomy with an inverted ILM flap was performed. After the surgery, the visual acuity improved to 0.2 with the closure of the FTMH confirmed by OCT. A FTMH in an eye with ocular toxoplasmosis was successfully closed by vitrectomy with an inverted ILM flap.

A Case of Conjunctival Amyloidosis with Repeated Subconjunctival Hemorrhage.

Conjunctival amyloidosis is a very rare disease, and its presence may be a sign of systemic amyloidosis. We present our ocular and systemic findings in a patient with conjunctival amyloidosis. A 43-year-old man had repeated subconjunctival hemorrhages (SCHs) for two years and was referred to the Chiba University Hospital. He had comprehensive ophthalmological and systemic examinations to determine the cause of the SCHs. His visual acuities were 1.2 OU, and the intraocular pressures were 13-14 mmHg OU. Magnetic resonance imaging was normal. Initially, the SCH was the only abnormality. After 3 months, the SCH had partially cleared, and a pink mass was detected in the superior area of the subconjunctiva. Partial biopsy and histopathological examinations showed a greenish birefringence and dichroism under polarized light illumination. The birefringence was located in amyloid fibers. Immunofixation electrophoresis detected λ-light chain abnormality in the ocular biopsy specimen but systemic examinations did not find any lesions. Multiple myeloma was ruled out, and the patient is being followed closely to detect any early signs of systemic amyloidosis. Because repeated SCHs might be initial signs of systemic amyloidosis, patients with conjunctival amyloidosis should be comprehensively examined for systemic amyloidosis because of its poor life prognosis.

Relapsing polychondritis with different types of ocular inflammations.

We were presented with two cases of relapsing polychondritis (RP) associated with different types of ocular inflammation. The first case was a 35-year-old man who had bilateral hyperemic conjunctiva and ocular pain, and was referred to Chiba University Hospital with a diagnosis of episcleritis refractory. He was treated with dexamethasone eye drops. He developed tinnitus, deafness in both ears, and left auriculitis. A left auricular biopsy showed an infiltration of lymphocytes surrounding the cartilage. He was diagnosed with RP and treated with 30 mg/day oral prednisolone. After tapering the prednisolone, the scleritis in both eyes improved. The second case was a 71-year-old man who was deaf in both ears and had bilateral scleritis. At the first visit to our hospital, his left eyelid and right auricula were reddish and swollen, and he reported some pain. He was treated with intravenous antibiotics, and the left orbital cellulitis quickly improved. However, he developed right scleritis and left gonitis. Magnetic resonance imaging showed bilateral posterior scleritis and right auricular perichondritis. Auricular biopsy showed an infiltration of lymphocytes into the periauricular tissue. He was diagnosed with RP, and 40 mg/day oral prednisolone was given and his symptoms improved. Although RP is rare, it is a life-threatening disease. Thus, ophthalmologists should consider RP in patients with both ocular and auricular inflammation.

Primary neuroendocrine carcinoma of ocular adnexa.

We present our findings in a case of primary neuroendocrine carcinoma (NEC) of the lacrimal gland and a case of primary Merkel cell carcinoma (MCC) of the eyelid. An 86-year-old man noticed a swelling of the left upper eyelid three months earlier. We performed excision biopsy and histopathological examination indicated that he had a primary NEC of the left lacrimal gland. He underwent chemotherapy followed by excision including the clinically visible margins and 50 Gy radiotherapy of the surgical margins. He had neither recurrence nor metastasis for 6 months since the last radiotherapy. An 80-year-old man noticed a nodule in the right upper eyelid and was referred to our hospital because the size was increasing rapidly. A complete surgical excision of the margins of the tumor was performed with histopathological confirmation of negative margins. The final diagnosis was a primary MCC of the right upper eyelid. After surgery, he underwent 50 Gy radiotherapy on the neck to prevent metastasis. No recurrence or metastasis was found for two years. Although primary NEC of the ocular adnexa is extremely rare, the tumor has high malignancy and readily metastasizes. Thus, combined therapy including surgery, radiotherapy, and/or chemotherapy is needed for complete management of NEC.

Refractory uveitis in patient with castleman disease successfully treated with tocilizumab.

Although multicentric Castleman disease is a rare but life-threatening disease, eye complications are extremely uncommon. We present a case of refractory uveitis accompanied with Castleman disease successfully treated with tocilizumab. A 58-year-old man with Castleman disease was introduced for refractory uveitis to Chiba University Hospital. Large cells were detected in the anterior chamber and increased vascular permeability of retinal vessels has been found in both eyes. Although the patient was treated with oral and eye drop steroid treatment, the uveitis symptoms had not decreased. The serum levels of CRP and IL-6 were increased. The level of IL-6 concentration in the anterior chamber was the same as the serum level of IL-6. The humanized anti-IL-6 receptor-antibody (tocilizumab) was administrated for the patient because of poor general condition. After tocilizumab treatment, large cells in the anterior chamber were undetectable and vascular permeability was improved in FA. The serum levels of CRP and IL-6 decreased and the general condition improved. The side effect of tocilizumab was not observed during the treatment. Tocilizumab treatment was significantly effective for uveitis accompanied with Castleman disease. Although it is extremely rare, uveitis accompanied with Castleman disease may be one of the hallmarks to consider tocilizumab treatment.

[Six cases of sterile endophthalmitis developed consecutively after intravitreal injection of bevacizumab].

PURPOSE: To report a series of 6 cases of sterile endophthalmitis that developed consecutively after an intravitreal injection of bevacizumab (IVB). PATIENTS AND METHODS: On April 13 and 14, 2009, we performed IVB for consecutive 12 eyes of 12 patients in a sterile condition. Within two days after injection, blurred vision without ocular pain, anterior chamber inflammation, and vitreous opacity were developed in 6 of the eyes of 6 patients. Hypopyon was not observed in any patient. Anterior chamber fluid from each eye and all syringes of bevacizumab that have been separated from the same bottle of same lot number were sent for bacterial culture examination. RESULTS: No bacterial colony was developed from the anterior chamber fluid of any of the patients nor from any of the syringes. Antibiotic treatment of all 6 patients was unsuccessful. The symptoms improved in all cases following treatment with topical corticosteroid within several days. CONCLUSIONS: Both the clinical course and the results of bacterial culture, lead to the possibility that our patients developed sterile endophthalmitis rather than infectious endophthalmitis. The exact causes of the endophthalmitis were not identified in our cases, but similar events are reported by several institutions, endophthalmitis following IVB needs to be considered a possibility.

Long-term success of intravitreal bevacizumab for choroidal neovascularization associated with choroidal osteoma.

PURPOSE: To describe a case of choroidal osteoma with choroidal neovascularization (CNV) that was successfully treated with two intravitreal injections of bevacizumab (IVB). DESIGN AND METHODS: Case report on a 12-year-old Japanese girl who presented with a sudden decrease in vision in her left eye. At the first visit, 2 days after the onset of her symptoms, her visual acuity (VA) in her left eye was 0.2. Ophthalmoscopy showed a hemorrhage of 5 disc diameters under the retinal pigment epithelium and a serous retinal detachment at the posterior pole of the left eye. These findings were confirmed by optical coherence tomography. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) showed several points of leakage around the fovea, which suggested a CNV. From these findings, the patient was diagnosed with choroidal osteoma with a CNV. The submacular hemorrhage was from the CNV associated with the choroidal osteoma. We treated her with two injections of 1.25 mg/0.05 mL IVB with a 4-month interval. RESULTS: The patient's VA in her left eye improved to 0.7, and this vision was maintained for 4 years. The CNV disappeared in the FA and ICGA images and no recurrence was observed after 4 years. CONCLUSION: Our findings indicate that IVB is effective in resolving CNV in eyes with an osteoma and prevents a decrease of vision in eyes with a choroidal osteoma with a CNV.

Early-stage mucinous sweat gland adenocarcinoma of eyelid.

We present the findings of an early-stage primary mucinous sweat gland adenocarcinoma in the lower eyelid of a Japanese patient. The patient was a 73-year-old man who had had a nodule on the left lower eyelid for two years. He was referred to our hospital with a diagnosis of a swollen chalazion. The clinical and histopathological records were reviewed and the mass was excised. Histopathological examination revealed a mucinous sweat gland adenocarcinoma. Postoperative magnetic resonance imaging and positron emission tomography excluded systemic metastases. After the histopathological findings, a complete surgical excision of the margins of the adenocarcinoma was performed, with histopathological confirmation of negative margins. After the final histopathological examination, the patient was diagnosed with a primary mucinous sweat gland adenocarcinoma of the left eyelid. Six months after the surgery, no recurrence has been observed. Because the appearance of mucinous sweat gland adenocarcinoma of the eyelid is quite variable, the final diagnosis can only be made by histopathological examination. A complete surgical excision is recommended.

A case of squamous cell carcinoma of conjunctiva as initial sign of systemic cancers.

The purpose of this report is to present the findings in a case of squamous cell carcinoma (SCC) of the conjunctiva which was the initial sign of systemic cancers. A 94-year-old woman without known systemic diseases developed a mass in her right conjunctiva. She was referred to our hospital 5 months after the onset. She was diagnosed with conjunctival SCC by biopsy. Systemic CT before the surgery revealed multiple liver lesions, lung legions, and a large mass surrounding the appendix. The patient requested the surgery, and the main aim of the surgery was cosmesis. Histopathological examinations of the specimen led us to the final diagnosis as SCC. She did not receive any other therapy because of her age. As no other surgical procedures were undertaken, it is uncertain as to whether the conjunctival lesion was primary or secondary. Although, it is extremely rare that SCC of the conjunctiva is the initial sign of systemic cancers, careful systemic examinations to find other cancers should be made.

Case of primary diffuse large B-cell lymphoma of lacrimal sac in a Japanese patient.

The purpose of this study was to determine the characteristics of primary diffuse large B-cell lymphoma (DLBCL) of the lacrimal sac. A 77-year-old man had epiphora of the right eye for three years. After visiting five clinics and hospitals, he was referred to our hospital, and the preoperative magnetic resonance imaging findings suggested a lacrimal sac mass. Dacryocysteography showed an obstruction of the right nasolacrimal duct, so we performed dacryocystectomy. After a histopathologic examination of the specimen, the patient was diagnosed with a DLBCL. Positron emission tomography scanning excluded metastases, and the final diagnosis was made of a primary DLBCL of the right lacrimal sac. He underwent radiotherapy with 30.6 Gray in total to the right lacrimal sac. After radiotherapy, no recurrence has been observed anywhere in his body for one year. Although a malignant lymphoma of the lacrimal sac is rare, clinicians should consider a primary malignant lymphoma in the differential diagnosis in patients with chronic dacryocystitis.

Relationship between chronic sclerosing dacryoadenitis with high level of IgG4 and Castleman disease.

The purpose of this study is to present a case of chronic sclerosing dacryoadenitis with high level of IgG4 in a patient diagnosed earlier with Castleman disease. A 79-year-old man noticed a swelling of his lower left jaw that was first seen 8 years earlier. He was diagnosed with Castleman disease from the histopathological examination of a biopsy of the submandibular gland. Since then, the size of the gland had not changed, and he had no systemic inflammatory signs or symptoms. He developed diplopia a year earlier, and CT scans showed bilateral swelling of the lacrimal glands. He was referred to our hospital for further examinations. The patient underwent partial dacryoadenectomy. From the histopathological examinations, he was diagnosed with chronic sclerosing dacryoadenitis with high level of the serum IgG4. He underwent oral steroid therapy and the swollen lacrimal glands were significantly improved. The results suggest that there may be pathological links between IgG4-related dacryoadenitis and Castleman disease.

Pattern visual evoked potentials in eyes with disc swelling due to cat scratch disease-associated neuroretinitis.

PURPOSE: To evaluate optic nerve function by pattern visual evoked potentials (VEPs) in eyes with optic disc swelling due to neuroretinitis associated with cat scratch disease (CSD). METHODS: Four eyes of four patients with marked optic disc swelling resembling optic neuritis but diagnosed serologically as CSD received systemic steroid treatment. VEPs elicited by black and white checkerboard stimuli created on a TV monitor were recorded before the treatment. RESULTS: The visual acuity (VA) in the affected eyes was decreased to 20/50 in two eyes and finger counting in two eyes at their initial visits. Ophthalmoscopic examination revealed neuroretinitis characterized by severe optic disc swelling, chorioretinal exudates, and macular edema in all eyes. Anti-Bartonella henselae serum antibody was markedly elevated in all patients confirming the diagnosis of CSD. The P100 of the transient VEPs was only mildly reduced without a delay in the implicit times in three eyes and only slightly delayed in the other eye. The steady-state VEPs were mildly reduced in two eyes and phase-reversed in other two eyes. The VA fully recovered after systemic steroid treatment in all patients. CONCLUSIONS: Although all examined patients showed marked swelling of the optic disc and visual decrease, the pattern VEPs were not affected as severely as in idiopathic optic neuritis. However, the degree of change of the pattern VEPs varied among patients.