To distinguish IgG4-related disease from seronegative granulomatosis with polyangiitis Rheumatolo... more To distinguish IgG4-related disease from seronegative granulomatosis with polyangiitis Rheumatology key message. IgG4-related disease might be an alternative diagnosis in limited granulomatosis with polyangiitis.
Purpose: Until now, three cases of growth of an orbital schwannoma during pregnancy have been pub... more Purpose: Until now, three cases of growth of an orbital schwannoma during pregnancy have been published. We aim to provide additional insight in the effect of pregnancy on orbital schwannomas. Methods: We present two additional cases of accelerated growth of orbital schwannomas during pregnancy and investigate receptor expression profiles for estrogen, progesterone, androgen, VEGF, EGF, FGF, PDGF-Rβ and ki-67 in the two pregnant cases and six non-pregnant cases. Results: Case 1: A 26-year-old woman developed unilateral exophthalmos during pregnancy, with normal visual acuity and ocular motility. During a subsequent pregnancy, again the exophthalmos progressed. MRI showed a mass suggestive of schwannoma. After delivery, resection of the lesion was performed through an anterior approach. Pathology confirmed schwannoma. The expression profile was positive for estrogen-and FGF receptors and ki-67, but negative for progesterone-, androgen-and other growth factor receptors. Case 2: A 24-year-old woman presented with diplopia and unilateral pain during pregnancy. She had normal visual acuity, but a mild exophthalmos and elevation deficit. MRI revealed an extraconal mass suggestive of schwannoma. After delivery, resection was performed through an anterior approach. Pathology confirmed the diagnosis. The expression profile was positive for ki-67, but negative for sex hormone-and growth factor receptors. In the six non-pregnant cases the expression profiles varied, with only one subject showing a strong expression of estrogen-, progesterone-and androgen receptors. Conclusions: Orbital schwannomas can experience growth during pregnancy. The underlying mechanism remains unclear as hormone-and growth factor expression profiles show no correlation to the pregnant state.
Treatment of uveal melanoma (UM) patients with metastatic disease is unfortunately limited. Twent... more Treatment of uveal melanoma (UM) patients with metastatic disease is unfortunately limited. Twenty percent of UM harbor a mutation in splicing factor gene SF3B1, suggesting that aberrant spliceosome functioning plays a vital role in tumorigenesis. Splicing inhibitors exploit the preferential sensitivity of spliceosome compromised leukemic cells to these compounds. We have studied the effect of splicing inhibitor E7107 using two UM cell lines and ex vivo cultured SF3B1 and BAP1 mutated primary UM tumor slices. These UM cell lines and ex vivo tumor slices were exposed for 24h to different concentrations of E7107. Tumor slices were stained with H&E and incubated with BAP1, MelanA, MIB-1 and caspase-3 antisera. E7107 exposed UM cell lines showed decreased cell viability and increased apoptosis with the largest effect sizes in SF3B1-mutated UM. A similar effect was observed upon exposure of E7107 on UM tumor slices. Additionally, RNA was isolated for transcriptome analysis and the type a...
International Forum of Allergy & Rhinology, 2022
Background: Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder and manif... more Background: Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder and manifestation in de paranasal and sphenoid sinus is well recognized. In this patient, IgG4-RD presented in an unusual manner with vision loss due to mucocele formation in the sphenoid sinus. Case Description: A 19-year-old man, with an unremarkable medical history, was referred with decreased vision in the left eye, headaches, and a sharp pain in the left orbit and ear. Compression of the left optic nerve due to a large mucocele caused papillary edema and emergency endoscopic marsupialization of the mucocele was performed. When the vision decreased again, a more extensive decompressing sphenoidotomy was performed. Histopathology showed IgG4-RD. Despite dexamethasone, the lesion expanded to the anterior skull base and the patient required repeat endoscopic surgery. After 3 months, a decrease in smell and vision warranted for a fourth extensive endoscopic decompressing surgery, complicated by a cerebrospinal fluid leak. Prednisone and later rituximab were commenced. Unfortunately, the patient reported a complete loss of vision after 4 months of rituximab due to increased mass effect on the optic nerve. An extensive combined craniofacial-endoscopic surgery was performed to remove the entire mucocele and to prevent further contralateral and intracranial progression. Methylprednisolone monthly was commenced to prevent further complications. Discussion: This case illustrates that in therapy-resistant sino-orbital IgG4-RD, extensive surgery might be necessary at an earlier stage. It may even be the only option to prevent irreversible damage to the surrounding tissues. A This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Purpose: Graves' orbitopathy (GO) is a rare condition in children often considered to be a less s... more Purpose: Graves' orbitopathy (GO) is a rare condition in children often considered to be a less severe condition than at an older age. The aim of our study was to analyse if there are any factors that distinguish paediatric from adult GO in order to provide guidelines for assessing and managing paediatric GO. Methods: Study design is a multicentre retrospective observational case series; 115 paediatric patients diagnosed with GO who visited our university medical centres in the Netherlands and Iran between 2003 and 2019 were submitted for complete ophthalmological examinations, serological testing and/or orbital imaging. Main outcome measures focussed on the natural course and clinical picture as well as medical and surgical treatment in paediatric GO. Results: Clinical findings included proptosis (n = 97; 84.3%), eyelid retraction (n = 77; 67%) and diplopia (n = 13; 11.3%). Ninety-two patients (80%) presented with mild disease, 21 (18.3%) with moderate-severe disease and two (1.7%) with severe GO. Five patients (4.3%) underwent intravenous glucocorticoids and 25 patients underwent orbital decompression surgery. Strabismus surgery due to primary involvement of extraocular muscles was performed in two patients (1.7%). Overall, rehabilitative surgical treatment was planned in 31 patients (26.9%) with inactive disease. Two patients experienced reactivation of the disease. Conclusion: Despite the fact that paediatric and adult GO are considered two separate entities, they might be the same disease with two different clinical phenotypes. Paediatric GO population presents with a comparable clinical picture regarding both soft tissue involvement and proptosis, which may require surgical intervention. Proptosis was present in the majority of paediatric GO patients. Orbital decompression was performed in 21.7% of patients.
PurposeTo demonstrate that long‐circulating PEGylated liposomal prednisolone is a safe and effect... more PurposeTo demonstrate that long‐circulating PEGylated liposomal prednisolone is a safe and effective therapy in patients with active moderate‐to‐severe Graves’ orbitopathy.MethodsOpen‐label, proof‐of‐concept, multicentre pilot study. Ten patients with moderate‐to‐severe Graves’s orbitopathy, who were euthyroid for at least three months. Long‐circulating PEGylated liposomal prednisolone 150 mg was administered intravenously twice, with 2‐week interval. Total follow‐up was 12 months, with visits at baseline, week 2, 6, 13, 26 and 52. Physical, laboratory and ophthalmological examinations were performed. Response to treatment was defined as a reduction in Clinical Activity Score by ≥2 points; palpebral aperture by ≥3 mm; soft tissue signs by ≥2 grades; exophthalmos by ≥2 mm; and motility by >8 degrees or improvement in diplopia score. A response was sustained when equally observed at weeks 6 and 13.ResultsOne patient achieved a sustained response according to the predetermined defin...
Mast cells and their products are likely to be involved in regulating orbital fibroblast activity... more Mast cells and their products are likely to be involved in regulating orbital fibroblast activity in Graves' Ophthalmopathy (GO). Histamine is abundantly present in granules of mast cells and is released upon mast cell activation. However, the effect of histamine on orbital fibroblasts has not been examined so far. Orbital tissues from GO patients and controls were analyzed for the presence of mast cells using toluidine blue staining and immunohistochemical detection of CD117 (stem cell factor receptor). Orbital fibroblasts were cultured from GO patients and healthy controls, stimulated with histamine and cytokines (IL-6, IL-8, CCL2, CCL5, CCL7, CXCL10 and CXCL11) were measured in culture supernatants. Also hyaluronan levels were measured in culture supernatants and hyaluronan synthase (HAS) and hyaluronidase (HYAL) gene expression levels were determined. In addition, histamine receptor subtype gene expression levels were examined as well as the effect of the histamine receptor-1 (HRH1) antagonist loratadine and NF-kB inhibitor SC-514 on histamine-induced cytokine production. Mast cell numbers were increased in GO orbital tissues. Histamine stimulated the production of IL-6, IL-8 and CCL2 by orbital fibroblasts, while it had no effect on the production of CCL5, CCL7, CXCL10, CXCL11 and hyaluronan. Orbital fibroblasts expressed HRH1 and loratadine and SC-514 both blocked histamine-induced IL-6, IL-8 and CCL2 production by orbital fibroblasts. In conclusion, this study demonstrates that histamine can induce the production of NF-kB controlled-cytokines by orbital fibroblasts, which supports a role for mast cells in GO.
To investigate the prevalence and prognostic value of SF3B1 and EIF1AX mutations in uveal melanom... more To investigate the prevalence and prognostic value of SF3B1 and EIF1AX mutations in uveal melanoma (UM) patients. Case series. Cohort of 151 patients diagnosed with and treated for UM. SF3B1 and EIF1AX mutations in primary tumors were investigated using whole-exome sequencing (n = 25) and Sanger sequencing (n = 151). For the detection of BAP1 mutations, a previously reported cohort of 90 patients was extended using BAP1 sequencing or immunohistochemistry. The status of SF3B1, EIF1AX, and BAP1 in tumors of patients were correlated to clinical, histopathologic, and genetic parameters. Survival analyses were performed for patients whose tumors had SF3B1, EIF1AX, and BAP1 mutations. Patients with tumors harboring EIF1AX mutations rarely demonstrated metastases (2 of 28 patients) and overall had a longer disease-free survival (DFS; 190.1 vs. 100.2 months; P < 0.001). Within the patient group with disomy 3, UM patients with an SF3B1 mutation had an increased metastatic risk compared wi...
Bulletin de la Société belge d'ophtalmologie, 2004
We present a patient who developed acute visual loss and light flashes at retrobulbar anesthesia ... more We present a patient who developed acute visual loss and light flashes at retrobulbar anesthesia for cataract extraction. Vision improved only slightly after cataract surgery. Although traumatic optic neuropathy was suspected, the patient was diagnosed one year later with an optic nerve sheath meningioma (ONSM). ONSM is a rare, slow growing, benign tumour with highly variable clinical features. Diagnosis is often delayed. This case report demonstrates the diagnostic difficulty of this tumour.
Purpose: To study the relation between signs of dry eye and acquired aponeurogenic blepharoptosis... more Purpose: To study the relation between signs of dry eye and acquired aponeurogenic blepharoptosis. Methods: Prospective case-control study in which 100 patients with uni-or bilateral acquired aponeurogenic blepharoptosis were matched for age and gender to 100 controls. The margin-reflex distance (MRD), the Schirmer-1 score, the duration of the tear film break up time (BUT), and the presence of any corneal staining with fluorescein were evaluated in both groups and compared. Data were analysed using either Fisher's exact test or linear regression. Results: The Schirmer-1 score was 510 mm in 36 patients versus 14 controls (p = 0.0005). It was 55 mm in 15 patients versus 5 controls (p = 0.03). Hard contact lenses were worn by 29 patients versus 4 controls (p = 0.000002), and soft contact lenses by 11 patients and 4 controls (p = 0.1). After exclusion of contact lens wearers from analysis, the Schirmer-1 score was 510 mm in 30 of the remaining 60 patients and in 17 of the remaining 92 controls (p = 0.00006). The tear BUT was 510 sec in 75 patients versus 71 controls (p = 0.6). Corneal staining was present in 25 patients versus 15 controls (p = 0.1). The score of the Schirmer-1 test and the MRD decreased with age in both groups. Conclusion: (1) Compared to matched controls, patients with acquired aponeurogenic blepharoptosis more often have a decreased aqueous tear production (as measured by a Schirmer-1 test). Although a low tear production may have a causative role in the etiology of acquired blepharoptosis, it may also be explained by a dampened reflex in blepharoptosis patients (2) With age, the MRD as well as the Schirmer-1 score decrease in both groups.
In this issue of Orbit, Pinilla et al. (2006) report on the long-term efficacy and shortand long-... more In this issue of Orbit, Pinilla et al. (2006) report on the long-term efficacy and shortand long-term complications of nasolacrimal stents in a series of 85 patients with complete nasolacrimal duct obstruction (NLDO). In 12% of patients, stent placement proved not possible, and in 43%, the stent was occluded after a mean follow-up of two years. Do these disappointing results really surprise us? Fluoroscopic lacrimal stent placement was introduced by Song and coworkers in the mid-90’s as a novel, minimally invasive technique for the treatment of NLDO (Song et al., 1994). It was thought that stenting would reduce the rate of re-obstruction compared with balloon dacryocystoplasty. At that time, the reported short-term success rates of up to 98% were very promising (Pinilla et al., 2006). The euphoria slightly subsided when patency rates at one year follow-up reportedly ranged between 5% and 85% (Pinilla et al., 2006). In several studies, inflammation and malplacement of the stent were identified as causes of early postoperative failure (Mandeville and Woog, 2002). In most series, patients were treated with steroids to reduce the inflammation induced by the trauma of stent placement. Lacrimal surgeons, who have removed nasolacrimal stents through external dacryocystorhinostomy (DCR), may confirm that the typical findings in longterm stent failure include a chronically inflamed lacrimal sac with granuloma formation and fibrosis in and around the stent and occlusive mucoid plugs in the stent’s lumen. Furthermore, scarring may fixate the stent to its surroundings, thus hampering (surgical) removal. Some reports indicated that periodic irrigation of the lacrimal system may reduce the rate of stent obstruction. The need for periodic irrigation considerably reduces the attractiveness of this treatment and probably does not prevent reobstruction in the long term. Even with recent suggestions to improve the design of the stent (Lanciego et al. 2003, Wilhem, 2004), the major drawbacks of inserting an allogenic stent in the non-sterile surrounding of a blocked NLD are not overcome. In complete NLDO, surgical DCR may prove to be much more patientfriendly, especially now the operation can be done in approximately 15 minutes under local anesthesia via the endonasal route, which does not cause a visible scar (Dolman, 2003). Pinalla et al. (2006) confirm an earlier observation by other workers (Yazici, 2002) that preceding nasolacrimal stent placement Address correspondence to Dion Paridaens, Rotterdam Eye Hospital, PO Box 70030, Rotterdam, 3000, LM, The Netherlands. Tel: 31 10 4017777; Fax: 31 10 4111747; E-mail: [email protected]
Purpose: To report on a one-stage technique for eyelid reconstruction with preservation of the ey... more Purpose: To report on a one-stage technique for eyelid reconstruction with preservation of the eyelid margin. Design: Prospective study. Methods: Five patients with small-to-intermediate full-thickness lower eyelid defects (n = 3) and upper eyelid defects (n = 2) after tumor excision. Defect size ranged from 5 to 7 mm vertically and from 7 to 12 mm horizontally. For eyelid reconstruction, a full-thickness pentagonal graft from the opposite lid was sutured into the full-thickness defect after removal of the orbicularis oculi muscle from the graft. The orbicularis muscle flap from the recipient eyelid was mobilized and brought in for vascular supply between tarsus and skin of the graft. The outcome after surgery was assessed using a subjective scoring system with 4 subsequent grades. Results: At 1 week postoperatively, adequate viability of the grafts was noted in all patients. After a mean follow-up of 13 months (range 3-33 months) the cosmetic and functional outcome was adequate in 1 case, good in 2 cases, and excellent in 2 cases. Conclusion: Reconstruction of small to intermediate full-thickness defects of both lower and upper eyelid with the "sandwich block"-technique is associated with a good functional and cosmetic outcome.
To report on a new 1-stage technique for eyelid reconstruction. Design: Retrospective interventio... more To report on a new 1-stage technique for eyelid reconstruction. Design: Retrospective interventional case series. Participants: Thirteen patients with shallow full-thickness lower eyelid defects (n ϭ 12) or a full-thickness upper eyelid defect (n ϭ 1) after tumor excision. Defect size ranged from 5 to 10 mm vertically and from 10 to 22 mm horizontally. Methods: For eyelid reconstruction, the orbicularis muscle adjacent to the defect was mobilized, incised vertically, and advanced. The inner surface was covered with a free tarsoconjunctival graft from the (ipsilateral or contralateral) upper lid, and the outer surface was covered with a free skin graft from the (ipsilateral or contralateral) upper eyelid. Main Outcome Measures: The outcome at 12 months after surgery was assessed using a subjective scoring system with 4 subsequent grades (poor, adequate, good, excellent). Results: After 5 days of patching, adequate viability of the grafts was noted in 11 of 13 patients. In 2 patients, partial necrosis of the skin graft developed, probably the result of hematoma. Complications included ectropion or lid retraction (3/13), granuloma (2/13), and notching (1/13). Two patients underwent additional block excision. The long-term outcome at 12 months after surgery was poor in 0 cases, adequate in 2 cases, good in 7 cases, and excellent in 4 cases. Conclusions: The sandwich technique for eyelid reconstruction comprises the use of an orbicularis oculi muscle advancement flap, which is covered with a free graft on both sides. It allows for 1-stage reconstruction of relatively shallow lower eyelid defects with a horizontal size of up to 70% of the total eyelid width and may be a 1-stage alternative to the modified Hughes flap in selected cases.
A case of an in situ adenocarcinoma of the lacrimal gland that developed in a recurring pleomorph... more A case of an in situ adenocarcinoma of the lacrimal gland that developed in a recurring pleomorphic adenoma is presented. Six years after incomplete resection of a pleomorphic adenoma, the patient complained of a progressive swelling of her right upper eyelid without pain or diplopia. An orbital computerized tomography scan showed an inhomogeneous mass in the right lacrimal gland region without bone involvement. After local excision of the in situ adenocarcinoma ex pleomorphic adenoma, the tumour has been in control for over 6 years.
Uveal melanoma (UM) is the most common primary intraocular tumor in the Western world. Cytogeneti... more Uveal melanoma (UM) is the most common primary intraocular tumor in the Western world. Cytogenetically, this tumor is characterized by typical chromosomal aberrations such as loss of 1p, 3, and 6q, and gain of 6p and 8q. Routinely, karyotyping and fluorescent in situ hybridization (FISH) on fresh tumor-biopsies are used to identify chromosomal changes. In addition, archival UM samples can be examined using comparative genomic hybridization (CGH). In the presented study, we used CGH on a series of 46 archival uveal melanomas to identify chromosomal changes. In 44 tumors aberrations were present and classic prognostic markers as loss of 1p (12 tumors, 26.1%), monosomy 3 (26 tumors, 56.5%), loss of 6q (10 tumors, 21.7%), and gain of chromosome arm 8q (27 tumors, 58.7%) were observed. Gain of chromosome arms 18q or 21q was found in three UMs. Multiplex ligation-dependent probe amplification (MLPA), a novel technique in UM, was performed to verify this low number of chromosome 18 and 21 abnormalities, but we could not confirm the previously reported gain of 18q11.2 and 21q11.2 as poor prognostic factors in UM.
Prednisone pulse therapy is used to treat active non-infectious orbital inflammatory disease to a... more Prednisone pulse therapy is used to treat active non-infectious orbital inflammatory disease to attain faster clinical improvement and to shorten the duration of prednisone treatment. This study addresses the use of intravenous methylprednisolone (IVMP) pulse therapy, in addition to oral prednisone (OP), in the treatment of severe idiopathic orbital inflammation (IOI). This was a multicentre retrospective cohort study. Patients with severe IOI treated with IVMP pulse and OP therapy (IVMP+OP) were compared with patients with IOI who were treated only with OP. Main outcome measures were duration of prednisone treatment, symptom-free outcome and complications. Between 2000 and 2007, 12 patients with severe IOI were treated with IVMP+OP and 15 patients were treated with OP only. The median treatment duration was 160 (range 34-680) days in the IVMP+OP group and 110 (range 27-730) days in the OP-only group. In patients who had severe IOI, 73% in the IVMP+OP group and 87% in the OP-only group were symptom-free after treatment. No patients developed complications related to prednisone therapy. In our study there was no advantage of treating patients with severe IOI with IVMP+OP in terms of shortened treatment duration, lower cumulative dose or decrease in persistent symptoms. We suggest that the indication of IVMP in the treatment of severe IOI is limited to speeding symptom relief and recovery from optic nerve dysfunction.
To distinguish IgG4-related disease from seronegative granulomatosis with polyangiitis Rheumatolo... more To distinguish IgG4-related disease from seronegative granulomatosis with polyangiitis Rheumatology key message. IgG4-related disease might be an alternative diagnosis in limited granulomatosis with polyangiitis.
Purpose: Until now, three cases of growth of an orbital schwannoma during pregnancy have been pub... more Purpose: Until now, three cases of growth of an orbital schwannoma during pregnancy have been published. We aim to provide additional insight in the effect of pregnancy on orbital schwannomas. Methods: We present two additional cases of accelerated growth of orbital schwannomas during pregnancy and investigate receptor expression profiles for estrogen, progesterone, androgen, VEGF, EGF, FGF, PDGF-Rβ and ki-67 in the two pregnant cases and six non-pregnant cases. Results: Case 1: A 26-year-old woman developed unilateral exophthalmos during pregnancy, with normal visual acuity and ocular motility. During a subsequent pregnancy, again the exophthalmos progressed. MRI showed a mass suggestive of schwannoma. After delivery, resection of the lesion was performed through an anterior approach. Pathology confirmed schwannoma. The expression profile was positive for estrogen-and FGF receptors and ki-67, but negative for progesterone-, androgen-and other growth factor receptors. Case 2: A 24-year-old woman presented with diplopia and unilateral pain during pregnancy. She had normal visual acuity, but a mild exophthalmos and elevation deficit. MRI revealed an extraconal mass suggestive of schwannoma. After delivery, resection was performed through an anterior approach. Pathology confirmed the diagnosis. The expression profile was positive for ki-67, but negative for sex hormone-and growth factor receptors. In the six non-pregnant cases the expression profiles varied, with only one subject showing a strong expression of estrogen-, progesterone-and androgen receptors. Conclusions: Orbital schwannomas can experience growth during pregnancy. The underlying mechanism remains unclear as hormone-and growth factor expression profiles show no correlation to the pregnant state.
Treatment of uveal melanoma (UM) patients with metastatic disease is unfortunately limited. Twent... more Treatment of uveal melanoma (UM) patients with metastatic disease is unfortunately limited. Twenty percent of UM harbor a mutation in splicing factor gene SF3B1, suggesting that aberrant spliceosome functioning plays a vital role in tumorigenesis. Splicing inhibitors exploit the preferential sensitivity of spliceosome compromised leukemic cells to these compounds. We have studied the effect of splicing inhibitor E7107 using two UM cell lines and ex vivo cultured SF3B1 and BAP1 mutated primary UM tumor slices. These UM cell lines and ex vivo tumor slices were exposed for 24h to different concentrations of E7107. Tumor slices were stained with H&E and incubated with BAP1, MelanA, MIB-1 and caspase-3 antisera. E7107 exposed UM cell lines showed decreased cell viability and increased apoptosis with the largest effect sizes in SF3B1-mutated UM. A similar effect was observed upon exposure of E7107 on UM tumor slices. Additionally, RNA was isolated for transcriptome analysis and the type a...
International Forum of Allergy & Rhinology, 2022
Background: Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder and manif... more Background: Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder and manifestation in de paranasal and sphenoid sinus is well recognized. In this patient, IgG4-RD presented in an unusual manner with vision loss due to mucocele formation in the sphenoid sinus. Case Description: A 19-year-old man, with an unremarkable medical history, was referred with decreased vision in the left eye, headaches, and a sharp pain in the left orbit and ear. Compression of the left optic nerve due to a large mucocele caused papillary edema and emergency endoscopic marsupialization of the mucocele was performed. When the vision decreased again, a more extensive decompressing sphenoidotomy was performed. Histopathology showed IgG4-RD. Despite dexamethasone, the lesion expanded to the anterior skull base and the patient required repeat endoscopic surgery. After 3 months, a decrease in smell and vision warranted for a fourth extensive endoscopic decompressing surgery, complicated by a cerebrospinal fluid leak. Prednisone and later rituximab were commenced. Unfortunately, the patient reported a complete loss of vision after 4 months of rituximab due to increased mass effect on the optic nerve. An extensive combined craniofacial-endoscopic surgery was performed to remove the entire mucocele and to prevent further contralateral and intracranial progression. Methylprednisolone monthly was commenced to prevent further complications. Discussion: This case illustrates that in therapy-resistant sino-orbital IgG4-RD, extensive surgery might be necessary at an earlier stage. It may even be the only option to prevent irreversible damage to the surrounding tissues. A This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Purpose: Graves' orbitopathy (GO) is a rare condition in children often considered to be a less s... more Purpose: Graves' orbitopathy (GO) is a rare condition in children often considered to be a less severe condition than at an older age. The aim of our study was to analyse if there are any factors that distinguish paediatric from adult GO in order to provide guidelines for assessing and managing paediatric GO. Methods: Study design is a multicentre retrospective observational case series; 115 paediatric patients diagnosed with GO who visited our university medical centres in the Netherlands and Iran between 2003 and 2019 were submitted for complete ophthalmological examinations, serological testing and/or orbital imaging. Main outcome measures focussed on the natural course and clinical picture as well as medical and surgical treatment in paediatric GO. Results: Clinical findings included proptosis (n = 97; 84.3%), eyelid retraction (n = 77; 67%) and diplopia (n = 13; 11.3%). Ninety-two patients (80%) presented with mild disease, 21 (18.3%) with moderate-severe disease and two (1.7%) with severe GO. Five patients (4.3%) underwent intravenous glucocorticoids and 25 patients underwent orbital decompression surgery. Strabismus surgery due to primary involvement of extraocular muscles was performed in two patients (1.7%). Overall, rehabilitative surgical treatment was planned in 31 patients (26.9%) with inactive disease. Two patients experienced reactivation of the disease. Conclusion: Despite the fact that paediatric and adult GO are considered two separate entities, they might be the same disease with two different clinical phenotypes. Paediatric GO population presents with a comparable clinical picture regarding both soft tissue involvement and proptosis, which may require surgical intervention. Proptosis was present in the majority of paediatric GO patients. Orbital decompression was performed in 21.7% of patients.
PurposeTo demonstrate that long‐circulating PEGylated liposomal prednisolone is a safe and effect... more PurposeTo demonstrate that long‐circulating PEGylated liposomal prednisolone is a safe and effective therapy in patients with active moderate‐to‐severe Graves’ orbitopathy.MethodsOpen‐label, proof‐of‐concept, multicentre pilot study. Ten patients with moderate‐to‐severe Graves’s orbitopathy, who were euthyroid for at least three months. Long‐circulating PEGylated liposomal prednisolone 150 mg was administered intravenously twice, with 2‐week interval. Total follow‐up was 12 months, with visits at baseline, week 2, 6, 13, 26 and 52. Physical, laboratory and ophthalmological examinations were performed. Response to treatment was defined as a reduction in Clinical Activity Score by ≥2 points; palpebral aperture by ≥3 mm; soft tissue signs by ≥2 grades; exophthalmos by ≥2 mm; and motility by >8 degrees or improvement in diplopia score. A response was sustained when equally observed at weeks 6 and 13.ResultsOne patient achieved a sustained response according to the predetermined defin...
Mast cells and their products are likely to be involved in regulating orbital fibroblast activity... more Mast cells and their products are likely to be involved in regulating orbital fibroblast activity in Graves' Ophthalmopathy (GO). Histamine is abundantly present in granules of mast cells and is released upon mast cell activation. However, the effect of histamine on orbital fibroblasts has not been examined so far. Orbital tissues from GO patients and controls were analyzed for the presence of mast cells using toluidine blue staining and immunohistochemical detection of CD117 (stem cell factor receptor). Orbital fibroblasts were cultured from GO patients and healthy controls, stimulated with histamine and cytokines (IL-6, IL-8, CCL2, CCL5, CCL7, CXCL10 and CXCL11) were measured in culture supernatants. Also hyaluronan levels were measured in culture supernatants and hyaluronan synthase (HAS) and hyaluronidase (HYAL) gene expression levels were determined. In addition, histamine receptor subtype gene expression levels were examined as well as the effect of the histamine receptor-1 (HRH1) antagonist loratadine and NF-kB inhibitor SC-514 on histamine-induced cytokine production. Mast cell numbers were increased in GO orbital tissues. Histamine stimulated the production of IL-6, IL-8 and CCL2 by orbital fibroblasts, while it had no effect on the production of CCL5, CCL7, CXCL10, CXCL11 and hyaluronan. Orbital fibroblasts expressed HRH1 and loratadine and SC-514 both blocked histamine-induced IL-6, IL-8 and CCL2 production by orbital fibroblasts. In conclusion, this study demonstrates that histamine can induce the production of NF-kB controlled-cytokines by orbital fibroblasts, which supports a role for mast cells in GO.
To investigate the prevalence and prognostic value of SF3B1 and EIF1AX mutations in uveal melanom... more To investigate the prevalence and prognostic value of SF3B1 and EIF1AX mutations in uveal melanoma (UM) patients. Case series. Cohort of 151 patients diagnosed with and treated for UM. SF3B1 and EIF1AX mutations in primary tumors were investigated using whole-exome sequencing (n = 25) and Sanger sequencing (n = 151). For the detection of BAP1 mutations, a previously reported cohort of 90 patients was extended using BAP1 sequencing or immunohistochemistry. The status of SF3B1, EIF1AX, and BAP1 in tumors of patients were correlated to clinical, histopathologic, and genetic parameters. Survival analyses were performed for patients whose tumors had SF3B1, EIF1AX, and BAP1 mutations. Patients with tumors harboring EIF1AX mutations rarely demonstrated metastases (2 of 28 patients) and overall had a longer disease-free survival (DFS; 190.1 vs. 100.2 months; P < 0.001). Within the patient group with disomy 3, UM patients with an SF3B1 mutation had an increased metastatic risk compared wi...
Bulletin de la Société belge d'ophtalmologie, 2004
We present a patient who developed acute visual loss and light flashes at retrobulbar anesthesia ... more We present a patient who developed acute visual loss and light flashes at retrobulbar anesthesia for cataract extraction. Vision improved only slightly after cataract surgery. Although traumatic optic neuropathy was suspected, the patient was diagnosed one year later with an optic nerve sheath meningioma (ONSM). ONSM is a rare, slow growing, benign tumour with highly variable clinical features. Diagnosis is often delayed. This case report demonstrates the diagnostic difficulty of this tumour.
Purpose: To study the relation between signs of dry eye and acquired aponeurogenic blepharoptosis... more Purpose: To study the relation between signs of dry eye and acquired aponeurogenic blepharoptosis. Methods: Prospective case-control study in which 100 patients with uni-or bilateral acquired aponeurogenic blepharoptosis were matched for age and gender to 100 controls. The margin-reflex distance (MRD), the Schirmer-1 score, the duration of the tear film break up time (BUT), and the presence of any corneal staining with fluorescein were evaluated in both groups and compared. Data were analysed using either Fisher's exact test or linear regression. Results: The Schirmer-1 score was 510 mm in 36 patients versus 14 controls (p = 0.0005). It was 55 mm in 15 patients versus 5 controls (p = 0.03). Hard contact lenses were worn by 29 patients versus 4 controls (p = 0.000002), and soft contact lenses by 11 patients and 4 controls (p = 0.1). After exclusion of contact lens wearers from analysis, the Schirmer-1 score was 510 mm in 30 of the remaining 60 patients and in 17 of the remaining 92 controls (p = 0.00006). The tear BUT was 510 sec in 75 patients versus 71 controls (p = 0.6). Corneal staining was present in 25 patients versus 15 controls (p = 0.1). The score of the Schirmer-1 test and the MRD decreased with age in both groups. Conclusion: (1) Compared to matched controls, patients with acquired aponeurogenic blepharoptosis more often have a decreased aqueous tear production (as measured by a Schirmer-1 test). Although a low tear production may have a causative role in the etiology of acquired blepharoptosis, it may also be explained by a dampened reflex in blepharoptosis patients (2) With age, the MRD as well as the Schirmer-1 score decrease in both groups.
In this issue of Orbit, Pinilla et al. (2006) report on the long-term efficacy and shortand long-... more In this issue of Orbit, Pinilla et al. (2006) report on the long-term efficacy and shortand long-term complications of nasolacrimal stents in a series of 85 patients with complete nasolacrimal duct obstruction (NLDO). In 12% of patients, stent placement proved not possible, and in 43%, the stent was occluded after a mean follow-up of two years. Do these disappointing results really surprise us? Fluoroscopic lacrimal stent placement was introduced by Song and coworkers in the mid-90’s as a novel, minimally invasive technique for the treatment of NLDO (Song et al., 1994). It was thought that stenting would reduce the rate of re-obstruction compared with balloon dacryocystoplasty. At that time, the reported short-term success rates of up to 98% were very promising (Pinilla et al., 2006). The euphoria slightly subsided when patency rates at one year follow-up reportedly ranged between 5% and 85% (Pinilla et al., 2006). In several studies, inflammation and malplacement of the stent were identified as causes of early postoperative failure (Mandeville and Woog, 2002). In most series, patients were treated with steroids to reduce the inflammation induced by the trauma of stent placement. Lacrimal surgeons, who have removed nasolacrimal stents through external dacryocystorhinostomy (DCR), may confirm that the typical findings in longterm stent failure include a chronically inflamed lacrimal sac with granuloma formation and fibrosis in and around the stent and occlusive mucoid plugs in the stent’s lumen. Furthermore, scarring may fixate the stent to its surroundings, thus hampering (surgical) removal. Some reports indicated that periodic irrigation of the lacrimal system may reduce the rate of stent obstruction. The need for periodic irrigation considerably reduces the attractiveness of this treatment and probably does not prevent reobstruction in the long term. Even with recent suggestions to improve the design of the stent (Lanciego et al. 2003, Wilhem, 2004), the major drawbacks of inserting an allogenic stent in the non-sterile surrounding of a blocked NLD are not overcome. In complete NLDO, surgical DCR may prove to be much more patientfriendly, especially now the operation can be done in approximately 15 minutes under local anesthesia via the endonasal route, which does not cause a visible scar (Dolman, 2003). Pinalla et al. (2006) confirm an earlier observation by other workers (Yazici, 2002) that preceding nasolacrimal stent placement Address correspondence to Dion Paridaens, Rotterdam Eye Hospital, PO Box 70030, Rotterdam, 3000, LM, The Netherlands. Tel: 31 10 4017777; Fax: 31 10 4111747; E-mail: [email protected]
Purpose: To report on a one-stage technique for eyelid reconstruction with preservation of the ey... more Purpose: To report on a one-stage technique for eyelid reconstruction with preservation of the eyelid margin. Design: Prospective study. Methods: Five patients with small-to-intermediate full-thickness lower eyelid defects (n = 3) and upper eyelid defects (n = 2) after tumor excision. Defect size ranged from 5 to 7 mm vertically and from 7 to 12 mm horizontally. For eyelid reconstruction, a full-thickness pentagonal graft from the opposite lid was sutured into the full-thickness defect after removal of the orbicularis oculi muscle from the graft. The orbicularis muscle flap from the recipient eyelid was mobilized and brought in for vascular supply between tarsus and skin of the graft. The outcome after surgery was assessed using a subjective scoring system with 4 subsequent grades. Results: At 1 week postoperatively, adequate viability of the grafts was noted in all patients. After a mean follow-up of 13 months (range 3-33 months) the cosmetic and functional outcome was adequate in 1 case, good in 2 cases, and excellent in 2 cases. Conclusion: Reconstruction of small to intermediate full-thickness defects of both lower and upper eyelid with the "sandwich block"-technique is associated with a good functional and cosmetic outcome.
To report on a new 1-stage technique for eyelid reconstruction. Design: Retrospective interventio... more To report on a new 1-stage technique for eyelid reconstruction. Design: Retrospective interventional case series. Participants: Thirteen patients with shallow full-thickness lower eyelid defects (n ϭ 12) or a full-thickness upper eyelid defect (n ϭ 1) after tumor excision. Defect size ranged from 5 to 10 mm vertically and from 10 to 22 mm horizontally. Methods: For eyelid reconstruction, the orbicularis muscle adjacent to the defect was mobilized, incised vertically, and advanced. The inner surface was covered with a free tarsoconjunctival graft from the (ipsilateral or contralateral) upper lid, and the outer surface was covered with a free skin graft from the (ipsilateral or contralateral) upper eyelid. Main Outcome Measures: The outcome at 12 months after surgery was assessed using a subjective scoring system with 4 subsequent grades (poor, adequate, good, excellent). Results: After 5 days of patching, adequate viability of the grafts was noted in 11 of 13 patients. In 2 patients, partial necrosis of the skin graft developed, probably the result of hematoma. Complications included ectropion or lid retraction (3/13), granuloma (2/13), and notching (1/13). Two patients underwent additional block excision. The long-term outcome at 12 months after surgery was poor in 0 cases, adequate in 2 cases, good in 7 cases, and excellent in 4 cases. Conclusions: The sandwich technique for eyelid reconstruction comprises the use of an orbicularis oculi muscle advancement flap, which is covered with a free graft on both sides. It allows for 1-stage reconstruction of relatively shallow lower eyelid defects with a horizontal size of up to 70% of the total eyelid width and may be a 1-stage alternative to the modified Hughes flap in selected cases.
A case of an in situ adenocarcinoma of the lacrimal gland that developed in a recurring pleomorph... more A case of an in situ adenocarcinoma of the lacrimal gland that developed in a recurring pleomorphic adenoma is presented. Six years after incomplete resection of a pleomorphic adenoma, the patient complained of a progressive swelling of her right upper eyelid without pain or diplopia. An orbital computerized tomography scan showed an inhomogeneous mass in the right lacrimal gland region without bone involvement. After local excision of the in situ adenocarcinoma ex pleomorphic adenoma, the tumour has been in control for over 6 years.
Uveal melanoma (UM) is the most common primary intraocular tumor in the Western world. Cytogeneti... more Uveal melanoma (UM) is the most common primary intraocular tumor in the Western world. Cytogenetically, this tumor is characterized by typical chromosomal aberrations such as loss of 1p, 3, and 6q, and gain of 6p and 8q. Routinely, karyotyping and fluorescent in situ hybridization (FISH) on fresh tumor-biopsies are used to identify chromosomal changes. In addition, archival UM samples can be examined using comparative genomic hybridization (CGH). In the presented study, we used CGH on a series of 46 archival uveal melanomas to identify chromosomal changes. In 44 tumors aberrations were present and classic prognostic markers as loss of 1p (12 tumors, 26.1%), monosomy 3 (26 tumors, 56.5%), loss of 6q (10 tumors, 21.7%), and gain of chromosome arm 8q (27 tumors, 58.7%) were observed. Gain of chromosome arms 18q or 21q was found in three UMs. Multiplex ligation-dependent probe amplification (MLPA), a novel technique in UM, was performed to verify this low number of chromosome 18 and 21 abnormalities, but we could not confirm the previously reported gain of 18q11.2 and 21q11.2 as poor prognostic factors in UM.
Prednisone pulse therapy is used to treat active non-infectious orbital inflammatory disease to a... more Prednisone pulse therapy is used to treat active non-infectious orbital inflammatory disease to attain faster clinical improvement and to shorten the duration of prednisone treatment. This study addresses the use of intravenous methylprednisolone (IVMP) pulse therapy, in addition to oral prednisone (OP), in the treatment of severe idiopathic orbital inflammation (IOI). This was a multicentre retrospective cohort study. Patients with severe IOI treated with IVMP pulse and OP therapy (IVMP+OP) were compared with patients with IOI who were treated only with OP. Main outcome measures were duration of prednisone treatment, symptom-free outcome and complications. Between 2000 and 2007, 12 patients with severe IOI were treated with IVMP+OP and 15 patients were treated with OP only. The median treatment duration was 160 (range 34-680) days in the IVMP+OP group and 110 (range 27-730) days in the OP-only group. In patients who had severe IOI, 73% in the IVMP+OP group and 87% in the OP-only group were symptom-free after treatment. No patients developed complications related to prednisone therapy. In our study there was no advantage of treating patients with severe IOI with IVMP+OP in terms of shortened treatment duration, lower cumulative dose or decrease in persistent symptoms. We suggest that the indication of IVMP in the treatment of severe IOI is limited to speeding symptom relief and recovery from optic nerve dysfunction.
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