Mika Noda

Conjunctival lymphoma arising from reactive lymphoid hyperplasia

Extra nodal marginal zone B-cell lymphoma (EMZL) of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH) of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU). Specimens from conjunctival tumors in the right eye, oculus dexter (OD), revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig) light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS), and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH) region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy.

Ectopic cilia: a histopathological study.

Cilia are normally found at the eyelid margin, while ectopic cilia are one or more lash follicles appearing in an abnormal position within the eyelid. We herein report two cases of cilia located in the palpebral conjunctiva. A 31-year-old female and a 46-year-old male presented with ectopic cilia in the superior palpebral conjunctiva. Histopathological study of the excised ectopic cilia and related lesions showed the cilia-related lesion to be located in the epithelial pit that contains goblet cells, which is consistent with the crypts of Henle. The hair follicle was surrounded by granulation tissue, while a dermal papilla and a hair matrix, which are known to produce hair follicles, did not exist in the excised tissue. While anterior ectopic cilia are congenital, ectopic cilia in the palpebral conjunctiva may be acquired, and these aberrant cilia are associated with crypts of Henle and chronic inflammation.

Intraocular neovascularization associated with choroidal ganglioneuroma in neurofibromatosis type 1.

Purpose. Neurofibromatosis type 1 (NF-1) complicates various tumors originating from the neural crest. The authors report a case of NF-1 presenting with globe enlargement and subretinal and choroidal neovascularization associated with choroidal ganglioneuroma. Methods. A 7-year-old boy with NF-1 had severe ocular pain OS. He has a medical history of congenital glaucoma OS. Left eye showed increased intraocular pressure, buphthalmos, corneal opacity, hyphema, and vitreous hemorrhage. Magnetic resonance imaging indicated prominent vitreous hemorrhage and a choroidal tumor. Enucleation was consequently performed OS. Results. Histopathologic diagnosis of the choroidal tumor was ganglioneuroma admixed with micro-vessels and melanocytes. There was a huge subretinal and choroidal fibrovascular membrane formation originating from the choroidal ganglioneuroma. Conclusions. Severe ocular pain in this patient was caused by intraocular neovascularization and subsequent increased eyeball content by vitreous hemorrhage associated with the choroidal tumor. In NF-1 with orbitofacial involvement, detection of intraocular tumor by imaging tests may predict tumor-associated severe ophthalmic complications.

Repair of blowout orbital floor fracture by periosteal suturing

The study objective was to evaluate the outcome of a periosteal suturing technique in eyes with orbital blowout fractures. Fifteen orbital floor fractures were classified into: type 1, linear fracture; type 2, middle fracture; and type 3, posterior fracture extending two‐thirds into the orbit. The feasibility of periosteal suturing without silicone plates or one of minimal size was determined. The improvement of ocular movements and surgical complications were evaluated. A complete suture of the torn periosteum without implanting a silicone plate was achieved in 2/2 (100%) type 1 cases, 5/7 (71%) type 2 cases and 0/6 (0%) type 3 cases. A partial fixation was achieved in 3/6 (50%) type 3 cases with an implantation of a silicone plate of approximate one‐third of the usual size in one case. Conventional surgery with silicone plates after failed periosteal suture was required in 2/7 (29%) type 2 cases and 3/6 (50%) type 3 cases. Eye movements were improved postoperatively in all eyes, and a complete range of eye movements was achieved in 6/7 (86%) cases with complete periosteal closure, 1/3 (33%) of cases with partial closure and 2/5 (40%) cases without closure. In conclusion, periosteal suturing can minimize the need for silicone plates especially for anterior or middle orbital floor factures.

Immunolocalization of Vascular Adhesion Protein-1 in Human Conjunctival Tumors

Objective: We analyzed the expression and immunolocalization of vascular adhesion protein (VAP)-1 in conjunctival tumors and normal conjunctival tissue of humans. Methods: Nine conjunctival tumors, including pyogenic granuloma and extranodal marginal zone B-cell lymphoma (EMZL), and 2 normal conjunctivas were analyzed by immunohistochemistry for VAP-1 and CD31 expression. Results: Immunoreactivity for VAP-1 was detected in the lumen of microvessels in pyogenic granuloma and in EMZLs. In contrast, normal bulbar conjunctival tissues demonstrated weak cytoplasmic immunoreactivity for VAP-1 in the blood vessels. Conclusions: The immunolocalization of VAP-1 varied in the histopathology of the conjunctiva, involving the pathology of inflammatory conjunctival disorders.

Decreased Proteasomal Activity Causes Photoreceptor Degeneration in Mice

PURPOSE To study the retinal degeneration caused by decreased proteasomal activity in β5t transgenic (β5t-Tg) mice, an animal model of senescence acceleration. METHODS β5t-Tg mice and age-matched littermate control (WT) mice were used. Proteasomal activities and protein level of poly-ubiquitinated protein in retinal extracts were quantified. Fundus images of β5t-Tg mice were taken and their features were assessed. For histologic evaluation, the thicknesses of inner nuclear layer (INL), outer nuclear layer (ONL), and photoreceptor outer segment (OS) were measured. For functional analysis, ERG was recorded under scotopic and photopic illumination conditions. Immunofluorescence (IF) staining and TUNEL were performed to investigate the mechanism of photoreceptor degeneration. RESULTS Chymotrypsin-like activity was partially suppressed in retinal tissues of β5t-Tg mice. Retinal degenerative changes with arterial attenuation were present in β5t-Tg, but not in WT mice. Inner nuclear layer thickness showed no significant change between β5t-Tg and WT mice at 1, 3, 6, and 9 months of age. By contrast, thicknesses of ONL and OS in β5t-Tg mice were significantly decreased at 3, 6, and 9 months compared with those in WT mice. Electroretinograms showed decrease of scotopic a-wave amplitude in β5t-Tg mice. The number of TUNEL-positive cells in ONL were significantly increased in β5t-Tg mice and colocalized with apoptosis-inducing factor, but not with cleaved caspase-3 and -9, indicating that the photoreceptor cell death was induced via a caspase-independent pathway. CONCLUSIONS The current data showed that impaired proteasomal function causes photoreceptor degeneration.

Solitary neurofibroma without neurofibromatosis in the superior tarsal plate simulating a chalazion

Dear Editor, Neurofibroma usually appears together with café au lait spots, iris nobules, and other tumors within the scope of neurofibromatosis von Recklinghausen type 1. Solitary neurofibroma is rare, especially in the eyelids, conjunctiva [1–3] or orbit [4]. Among the few reports of isolated neurofibroma in eyelids and conjunctiva there have been just two Japanese cases. One was a 72-year-old female, where a small tumor in the left upper eyelid margin recurred despite repeated resections. The other was a 60-year-old male with two isolated tumors in the lateral canthus and bulbar conjunctiva which bulged spherically. Among the important differential diagnoses we have to think about a chalazion, a meibomian gland ademocarcinoma and a schwannoma [5–7]. This article describes the first case of isolated neurofibroma in the eyelid tarsal plate, and a characteristic useful for diagnosis. The patients medical history, pathological findings, treatment, and outcome are discussed. A 57-year-old woman presented to our institution in November 2007 with a 5-year history of progressive right upper eyelid swelling. She had suffered from malignant lymphoma (diffuse large B-cell lymphoma) 4 years previously, with complete remission following a course of chemotherapy. On ocular examination, no other abnormalities were evident. The external inspection revealed a slightly spherically bulged tumor of the upper eyelid that resembled a chalazion covered by normal-looking skin (Fig. 1a), a characteristic oval-shaped yellowish tumor with numerous centripetal vessels present in the conjunctiva on the inside of the lid (Fig. 1b). Fluorescein staining revealed the tumor elevated from the tarsal plate surrounded by a shallow furrow (Fig. 1c). The tumor, 4× 5 mm in diameter and 1 mm in thickness, had an elastic hard texture. A biopsy showed no evidence of malignant lymphoma. The findings were compatible with neurofibroma, apart from lack of von Recklinghausen disease indicators such as café-au-lait spots, iris nodules or other neurofibromas. To relieve discomfort of compression, in May 2008 the tumor was resected en bloc, and remaining tarsal and palpebral soft tissues were sutured without lid deformity. Hematoxylin and eosin staining revealed that the tumor occupied the full thickness of the tarsal plate, surrounded by normal acini of the meibomian glands. The tumor was covered by a normal palpebral conjunctival epithelium (Fig. 2a). Numerous cells with spindle-shaped nuclei were arranged irregularly (Fig. 2b) in collagen fibers stained blue with Masson’s trichrome. In neurofibroma, S-100 protein positive cells, CD34 positive cells, and mast cells are usually intermingled in various proportions. These cell types were present in this case (two are shown in Fig. 2c,d); accordingly, solitary neurofibroma Presentation at a conference: The 62 Annual Congress of Japan Clinical Ophthalmology (2008)

Dehiscence of levator aponeurosis in ptosis after sub-Tenon injection of triamcinolone acetonide

OBJECTIVE To report the incidence, intraoperative findings, and surgical outcome of secondary ptosis that developed after a sub-Tenon injection of triamcinolone acetonide (TA). STUDY DESIGN Retrospective, cross-sectional study. PARTICIPANTS One hundred forty-seven cases with a total of 286 sub-Tenon TA injections. METHODS The medical records of 163 eyes of 147 cases treated with a sub-Tenon injection of 10 mg or 20 mg TA were reviewed. The incidence of secondary ptosis (palpebral fissure >2 mm narrower than that of the fellow eye) after a sub-Tenon TA injection was determined. The preoperative levator function and margin reflex distance (MRD) of the affected eyes, and the intraoperative findings in eyes that underwent reconstructive surgery, were evaluated. RESULTS Eight eyes (5%) developed secondary ptosis after the injection and 6 eyes were treated by reconstructive surgery. The preoperative levator function of the affected eyes did not differ from that of the fellow eyes. Intraoperatively, no septal disruption or fat herniation was noted, but an aponeurotic disinsertion was identified and repaired with an advancement of the leading edge to the anterior tarsal plate. The surgery led to satisfactory results, with improvement of the MRD from -1.3 (SD 1.5) mm preoperatively to 2.3 (SD 0.5) mm postoperatively (p = 0.027). Additional sub-Tenon TA injections were required in 2 eyes after eyelid surgery but the ptosis did not worsen. CONCLUSIONS A sub-Tenon TA injection can occasionally cause ptosis by inducing a disinsertion of the levator aponeurosis. However, surgical reconstruction can lead to successful resolution of the ptosis.

Expression of Vascular Endothelial Growth Factor in Human Ocular Adnexal Lymphoma

PURPOSE To examine the expression of VEGF in extranodal marginal zone B-cell lymphoma (EMZL) and reactive lymphoid hyperplasia (RLH) of human ocular adnexa, and analyze the correlation with the intratumoral microvessel density (MVD). METHODS Twenty-two EMZL and 16 RLH tissues were examined in this study. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with antibodies against VEGF and CD20. Vascular endothelial growth factor expression was analyzed using the ELISA and RT-PCR in the EMZL tissues. Microvessel density was determined based on the immunoreactivity for anti-CD34 antibody. RESULTS Vascular endothelial growth factor immunoreactivity was detected in the cytoplasm of lymphoid cells in EMZL and RLH. ELISA and RT-PCR confirmed VEGF protein and mRNA expressions in the EMZL tissue, respectively. Vascular endothelial growth factor-immunopositive rate in B-cells was significantly higher in 12 conjunctival EMZLs than four RLHs (P < 0.01) and 10 orbital EMZLs than 12 RLHs (P < 0.05). The MVD showed a significant positive correlation with the VEGF-immunopositive rate in conjunctival and orbital EMZLs. CONCLUSIONS This study demonstrated increased VEGF expression in human conjunctival and orbital EMZL compared with that in RLH, suggesting that VEGF plays a significant role in the pathogenesis and tumor angiogenesis of ocular adnexal lymphoma.

Oxidative stress in the levator aponeurosis in Asian involutional blepharoptosis.

Purpose: To analyze the histopathology and expression of 8-hydroxydeoxyguanosine (OHdG), a marker of oxidative stress, in the levator aponeurosis tissues of involutional aponeurotic and congenital blepharoptosis patients, and adult subjects with no history of blepharoptosis. Methods: Fourteen and 4 levator aponeurosis tissues obtained from Asian patients with involutional and congenital blepharoptosis and 3 normal adult tissues were examined. All tissues were fixed in 4% paraformaldehyde, embedded in paraffin, and then submitted for hematoxylin and eosin staining and immunohistochemistry with anti-8-OHdG antibody. Results: The levator aponeurosis tissues contained spindle smooth muscle fibers and striated muscles. Nuclear immunoreactivity for 8-OHdG was noted in striated and smooth muscle cells in all the tissues. The 8-OHdG-positive rate was significantly lower in congenital blepharoptosis than involutional blepharoptosis (p < 0.05). Moreover, the number of 8-OHdG-positive striated muscle cells was significantly higher in the involutional blepharoptosis than normal tissues (p < 0.05). In contrast, there was a rare positive 8-OHdG-immunoreactivity of smooth muscle cells in the aponeurotic tissues of the involutional blepharoptosis patients. Conclusions: Levator aponeurosis in involutional aponeurotic blepharoptosis tissues showed oxidative stress in the muscle, indicating that oxidative stress plays a potential role in the pathologic study of the disease.