Surgical correction of involutional lower lid entropion with lateral canthal eyelid block excision and imbrication of the capsulopalpebral ligament using non-buried non-resorbable imbricating sutures versus buried resorbable imbricating sutures.

PURPOSE: To compare the results of surgical correction of involutional lower eyelid entropion using either buried resorbable imbricating sutures or non-buried non-resorbable sutures that were removed after five to seven days. METHODS: Retrospective analysis of a two-surgeon series. Analysis of the charts of patients surgically treated for involutional lower eyelid entropion between January 2011 and December 2014 with a minimum follow-up of 12 months. MAIN OUTCOME MEASURES: Recurrence rate, postoperative complications. RESULTS: We included 281 eyelids of 240 patients. Of these, 89 eyelids had been treated with buried resorbable imbricating sutures (surgeon WvdB) and 192 with non-buried non-resorbable sutures (surgeon DP). Of the 281 eyelids, 77 eyelids had undergone previous entropion surgery. In the buried resorbable suture group (group R), the mean follow-up was 30 months (range 12 to 61 months) versus 39 months (range 14 to 60 months) in the non-buried non-resorbable group (group NR) (p = 0.07). With a follow-up of up to 18 months, the recurrence rate was 2.2% in group R and 4.2% in group NR (p = 0.73). With a similar follow-up, the recurrence rate was 3.9% after primary surgery versus 2.6% in recurrent cases (p = 0.73). Minor postoperative complications and side-effects were seen in 5.3% (15/281). CONCLUSION: We found no difference in the recurrence rate between the use of buried resorbable imbricating sutures and non-buried non-resorbable sutures and between primary versus recurrent cases. We conclude that we can safely use buried resorbable imbricating sutures in involutional entropion. It yields comparable results and omits the need for suture removal.

Histamine induces NF-κB controlled cytokine secretion by orbital fibroblasts via histamine receptor type-1.

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-κB 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-κB controlled-cytokines by orbital fibroblasts, which supports a role for mast cells in GO.

The tyrosine kinase inhibitor dasatinib effectively blocks PDGF-induced orbital fibroblast activation.

BACKGROUND: Graves' ophthalmopathy (GO) remains hard to treat. Excessive orbital fibroblast activation by platelet-derived growth factor (PDGF)-BB contributes to GO. The tyrosine kinase inhibitors (TKIs) imatinib mesylate and dasatinib both target PDGF-receptor tyrosine kinase activity, albeit with a different potency. We compared the efficacy of these TKIs on PDGF-BB-induced proliferation, and on cytokine and hyaluronan production by orbital fibroblasts. Also the capacity of dasatinib to suppress GO-associated gene expression in orbital tissue was examined. METHODS: Orbital fibroblasts from four GO patients and five control subjects were used. The efficacy of the two TKIs was tested by: 1) pre-incubating orbital fibroblasts overnight with different TKI concentrations, followed by 24 h stimulation with PDGF-BB, 2) adding TKI and PDGF-BB simultaneously to the orbital fibroblasts in 24 h cultures. Proliferation was assessed by colorimetric assay. Hyaluronan and cytokine production were measured by ELISA. Furthermore, orbital tissue was obtained from a patient with active GO, and the effect of dasatinib on the expression levels of HAS2-, CCL2-, IL6-, and IL8-mRNA expression was examined by real-time quantitative PCR. RESULTS: Pre-incubation of orbital fibroblasts with imatinib mesylate or dasatinib resulted in significant and dose-dependent inhibition of PDGF-BB-induced orbital fibroblast proliferation, and hyaluronan and cytokine production. Dasatinib exhibited these effects at far lower concentrations. The same results were observed in the setting where TKI and PDGF-BB treatments were commenced simultaneously. In orbital tissue from active GO, dasatinib significantly suppressed HAS2-, CCL2-, IL6- and IL8-mRNA levels. CONCLUSION: Dasatinib may be a promising alternative to high-dose steroids in the treatment of GO.

Results of surgical correction of upper eyelid retraction in Graves' Orbitopathy.

INTRODUCTION: Anterior levator disinsertion/reinsertion and Müllerectomy (ALDM) is generally performed to correct upper eyelid retraction in patients with Graves' orbitopathy (GO). We studied the outcome of this procedure and its correlation with clinical parameters. PATIENTS AND METHODS: Retrospective analysis of results of ALDM in 305 consecutive euthyroid patients with burnt-out GO treated in our hospital between 1 January 2000 and 1 January 2016. From the patient files, we recorded data on age, gender, laterality of surgery, smoking history and previous interventions. For outcome analysis, we used a qualitative scoring system with subdivision into three categories (good (MRD-1 of 4-5 mm, smooth upper eyelid contour and left-right difference of < 1 mm); acceptable (MRD-1 of 3-<4 or> 5-6 mm), smooth upper eyelid contour and left-right difference of < 2 mm; poor: if none of the above criteria was met). We analysed the outcome per eyelid as well as per patient. RESULTS: Of the 305 patients (471 eyelids), 166 underwent bilateral and 139 unilateral surgery. Regarding eyelids, the outcome of surgery was good in 71.6% (337/471) acceptable in 15.7% (74/471) and poor in 12.7% (60/471). Regarding patients, the outcome was good in 64.3% (196/305), acceptable in 15.7% (48/305) and poor in 20% (61/305). Concerning bilateral and unilateral surgery, the outcome was good in 60.8% (101/166) and acceptable in 16.9% (28/166) of patients after bilateral surgery, and good in 68.3% (95/139) and acceptable in 14.4% (20/139) of the patients after unilateral surgery (p = 0.17). Reoperation was performed in 16% (75 of 471) of eyelids and in 22 % (66 of 305) of patients. After secondary surgery, the cumulative success percentage was good in 78.6% (370/471) of eyelids and in 79% (241/305) of patients. We found no relation between surgical outcome and any other studied parameter, such as age, gender, smoking history and previous intervention such as extraocular muscle surgery and/or orbital decompression. CONCLUSION: Correction of upper eyelid retraction yields a good result in 64.3% of patients and 71.6% of eyelids. With one additional procedure, the procedure proved was successful in 79% of patients and eyelids. We found no relation between the outcome of surgery and any other parameter, such as previous disease severity, previous interventions or smoking history. For comparative analysis, we recommend to report the outcome per patient rather than per eyelid.

Retrospective study in 608 cases on the rate of surgical site infections after orbital surgery without prophylactic systemic antibiotics.

OBJECTIVE: To determine postoperative surgical site infection (SSI) rates in three separate patient groups who underwent orbital surgery without prophylactic systemic antibiotics. STUDY DESIGN: Single-centre retrospective descriptive case series. STUDY POPULATION: We studied the notes of 639 consecutive patients who had undergone orbital surgery in our hospital from 2009 through 2013. All patients belonged to either of three groups: (1) clean orbital surgery (n=226); (2) clean orbital surgery with implant (n=290); (3) clean-contaminated surgery (n=92). Thirty-one patients were excluded. RESULTS: Of the total of 608 patients, without systemic antibiotic prophylaxis, only five were diagnosed with SSI 5/608 (0.82%): 1/226 in the 'clean' group, 3/290 in the 'clean-with-implant' group and 1/92 in the 'clean-contaminated' group. All five patients with SSI were effectively treated with antibiotics. CONCLUSION: In this study 'clean', 'clean-with-implant' and 'clean-contaminated' orbital surgery was safely performed without prophylactic antibiotics. Where postoperative infection did occur, the patients were effectively treated with systemic antibiotics. We suggest to restrict the administration of systemic antibiotic prophylaxis in orbital surgery.

Orbicularis muscle advancement flap combined with free posterior and anterior lamellar grafts: a 1-stage sandwich technique for eyelid reconstruction.

PURPOSE: 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 = 12) or a full-thickness upper eyelid defect (n = 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.

Silicone intubation with or without balloon dacryocystoplasty in acquired partial nasolacrimal duct obstruction.

PURPOSE: To examine if the addition of (antegrade) balloon dacryocystoplasty to bicanalicular silicone intubation affects the success rate in adults with incomplete nasolacrimal duct (NLD) obstruction. DESIGN: Prospective, randomized trial. METHODS: Seventy eyes of 70 patients with incomplete NLD obstruction and severe epiphora (Munk score grade 3 or 4) were treated randomly with dacryocystoplasty (Lacricath) and silicone intubation (Ritleng; n = 35, group 1; mean age, 54.4 years; standard deviation [SD], 11.8 years) or silicone intubation alone (n = 35, group 2; mean age, 53.5 years; SD, 13.1 years; P > .05). The silicone tubes were removed after, on average, three months. At the visit, we assessed the grade of epiphora using the Munk score. Complete success was defined as Munk score of 0 or 1, partial success was defined as Munk score of 2, and failure was defined as Munk score of 3 or 4. Long-term Munk scores were obtained through a telephone survey nine to 76 months after surgery (mean, 43.4 in group 1 and 34.9 in group 2; P > .05). RESULTS: Complete success was reported by 18 patients (52%) in group 1 and by 20 patients (57%) in group 2. Partial success was reported by one patient in group 1 and by one patient in group 2. No improvement was reported by 15 patients (44%) in group 1 and by 14 patients (40%) in group 2. Differences between the two groups proved to be not significant (P = .8, exact Chi-square trend test). CONCLUSIONS: In our patients with acquired partial NLD obstruction, treatment with a combination of antegrade dacryocystoplasty and silicone intubation was not associated with a higher success rate compared with treatment with silicone intubation alone.

A single- versus double-layered closure technique for full-thickness lower eyelid defects: a comparative study.

PURPOSE: To compare a simplified, single-layered closure technique with a double-layered closure technique in lower eyelid reconstruction following full-thickness pentagonal block excision. METHODS: We conducted a retrospective, non-randomized, interventional case-control study. Clinical data of consecutive patients treated with primary closure of a full-thickness lower eyelid defect between 2011 and 2014 were analysed. In group A, the defect was closed in one layer, using non-absorbable polypropylene sutures. In group B, the defect was closed in two layers, using absorbable polyglactin acid sutures. In both techniques, we rarely used a grey line suture to adjust the eyelid margin. We assessed notching, wound dehiscence and other complications, as reported at 2 months after surgery. RESULTS: We included 188 eyelids from 186 patients. In group A, we included 82 eyelids and in group B 106 eyelids. We noted no difference in notching (p = 0.96) whilst wound dehiscence had not occurred in either group. Subcutaneous granuloma formation had been noted in 0 cases in group A, versus 4 in group B (p = 0.08). Mild redness of the scar was seen in 2 cases in group A, versus 5 in group B (p = 0.41). A grey line suture was placed in 6 cases in group A (7.3%), versus 4 cases in group B (3.8%; p = 0.28). CONCLUSION: Both single- and double-layered closure techniques are safe and effective methods for primary closure of full-thickness lower eyelid defects. In both techniques, a grey line suture was rarely required to adjust the eyelid margin.

Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts.

Orbital fibroblast activation is a central pathologic feature of Graves' Ophthalmopathy (GO). Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been proposed to contribute to GO, but their effects on orbital fibroblasts are largely unknown. We found that bFGF stimulated proliferation and hyaluronan production, but not IL-6 production by orbital fibroblasts, while VEGF hardly affected orbital fibroblast activity. Remarkably, co-stimulation of orbital fibroblasts with bFGF and PDGF-BB synergistically enhanced IL-6 and hyaluronan production and displayed an additive effect on proliferation compared to either bFGF or PDGF-BB stimulation. Nintedanib, a FGF- and PDGF-receptor targeting drug, more efficiently blocked bFGF + PDGF-BB-induced IL-6 and hyaluronan production than dasatinib that only targets PDGF-receptor. In conclusion, bFGF may contribute to orbital inflammation and tissue remodeling in GO, especially through synergistic interaction with PDGF-BB. Multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO.

Blepharoptosis and upper eyelid swelling due to lipogranulomatous inflammation caused by silicone oil.

PURPOSE: Report of two patients who presented with unilateral upper eyelid swelling and ptosis 1 and 8 years, respectively, after vitreoretinal surgery with intraocular silicone oil. DESIGN: Report of two cases. METHODS: In the first case, the oil was still present in the eye. In the second case, the intraocular oil and an epibulbar buckle had been removed 7 years earlier. RESULTS: Histopathology of upper eyelid skin and preaponeurotic fat revealed lipogranulomatous inflammation. CONCLUSIONS: Leakage of intraocular silicone oil into the eyelid tissues may cause an inflammatory reaction resulting in eyelid swelling and ptosis. We presume that in the first patient, silicone oil had leaked from the eye during or after surgery; in the second patient, silicone oil had probably been left behind in the space previously occupied by the epibulbar buckle.

Platelet-Derived Growth Factor-BB Enhances Adipogenesis in Orbital Fibroblasts.

PURPOSE: Platelet-derived growth factor (PDGF)-BB has been identified as important factor in pathogenesis of Graves' ophthalmopathy (GO). It stimulates proliferation, cytokine, and hyaluronan production, and thyrotropin receptor expression by orbital fibroblasts. Therefore, the PDGF-pathway has been proposed as a target for pharmacological intervention in GO. However, increased adipogenesis is another major pathological characteristic of GO and it is unknown whether this is affected by PDGF-BB. The aim of this study was to investigate the effect of PDGF-BB on adipocyte differentiation by orbital fibroblasts. METHODS: Orbital fibroblasts from five healthy controls and nine GO patients were collected. Adipogenesis was induced by culturing orbital fibroblasts in differentiation medium, either in the presence or absence of PDGF-BB. Adipogenesis was determined by Oil-Red-O staining, triglyceride measurement, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA expression. RESULTS: Platelet-derived growth factor-BB significantly enhanced adipocyte differentiation by orbital fibroblasts (Oil-Red-O staining [P < 0.0001], triglyceride measurement [P < 0.05], and PPAR-γ mRNA expression [P < 0.05]). It enhanced IL-6 production early during differentiation, but the effect of PDGF-BB on adipogenesis was independent of autocrine IL-6 signaling as it was not abrogated by IL-6-receptor-α neutralizing antibody. The clinically applicable tyrosine kinase inhibitor dasatinib and tyrphostin AG1296, which both block PDGF receptor tyrosine kinase activity, inhibited PDGF-BB-enhanced adipogenesis (P < 0.05) in orbital fibroblasts. Moreover, dasatinib reduced PPAR-γ mRNA expression in cultured GO orbital tissue. CONCLUSIONS: Platelet-derived growth factor-BB enhances adipogenesis in orbital fibroblasts, and, thus, may contribute to adipose tissue expansion in GO. Therefore, the PDGF-signaling cascade may represent a target of therapy to interfere with adipogenesis in GO.

Not only hard contact lens wear but also soft contact lens wear may be associated with blepharoptosis.

OBJECTIVE: The authors attempt to establish an association between prolonged hard and soft contact lens wear and ptosis. DESIGN: Single-center retrospective consecutive series. PARTICIPANTS: All patients between 18 and 50 years of age who were diagnosed with unilateral or bilateral ptosis between January 2002 and December 2005 (35 patients). METHODS: In a retrospective consecutive series, we included all patients between 18 and 50 years of age, with unilateral or bilateral ptosis between January 2002 and December 2005. Patients with congenital ptosis, ophthalmic surgery or disease, trauma, giant papillary conjunctivitis, unknown duration of contact lens wear, or muscular or neurologic disorders were excluded. We compared this study group to a Dutch reference population (the total underlying population from which the ptosis cases derive). RESULTS: The group included 35 patients: 20 (57%) (ages 18 to 50 years, average 37 years) had been wearing hard contact lenses for, on average, 17.6 years (range 6 to 27 years); 9 (26%) (ages 18 to 45 years, average 30 years) had been wearing soft contact lenses for, on average, 9 years (range 1.5 to 20 years); and 6 (17%) (ages 23 to 39 years, average 33 years) had no history of contact lens wear. The odds ratio for soft contact lenses was 14.7 (4.2 to 50.7; CI = 95) and for hard contact lenses 97.8 (22.5 to 424). CONCLUSIONS: This study suggests that not only hard contact lens wear but also soft contact lens wear may be associated with ptosis.

Azathioprine and prednisone combination treatment for adult periocular and orbital xanthogranulomatous disease.

PURPOSE: To report the authors' experience with azathioprine and prednisone combination for adult periocular and orbital xanthogranulomatous disease. METHODS: We identified 13 adults with histology-proven periocular or orbital xanthogranuloma in two tertiary referral orbital centres from 1984 to 2008. Patient records were reviewed and data collected on orbital localization, immune dysfunction, applied treatment and outcome. RESULTS: Five patients with periocular or orbital xanthogranulomatous disease were fully treated with prednisone and azathioprine combination, which resulted in stabilization in two and regression in three. Two other patients had to discontinue azathioprine because of side-effects. Of the non-fully treated prednisone/azathioprine patients, four out of eight progressed. CONCLUSION: In adult periocular and orbital xanthogranuloma, combined treatment with prednisone and azathioprine yields adequate immunosuppression, often for a prolonged period of time.

Whole orbital tissue culture identifies imatinib mesylate and adalimumab as potential therapeutics for Graves' ophthalmopathy.

BACKGROUND AND AIMS: Biologicals and small inhibitory molecules are used to treat inflammatory diseases, but their efficacy varies upon clinical application. Using a whole orbital tissue culture system, we tested the potential efficacy of imatinib mesylate (a tyrosine kinase inhibitor that blocks platelet-derived growth factor (PDGF)-receptor, c-Abl and c-Kit activity) and adalimumab (an anti-TNF-α antibody) for the treatment of Graves' ophthalmopathy (GO). METHODS: Orbital fat tissue from GO patients (n=10) was cultured with or without imatinib mesylate or adalimumab. PDGF-B and tumour necrosis factor (TNF)-α mRNA expression levels were determined in the primary orbital tissue, and interleukin (IL)-6 and hyaluronan were measured in tissue-culture supernatants. RESULTS: Imatinib mesylate significantly (p=0.005) reduced IL-6 and hyaluronan production. The inhibition of hyaluronan production correlated positively and significantly (p<0.05) with the PDGF-B mRNA level in the primary tissue. Adalimumab also significantly (p=0.005) reduced IL-6 production. The amount of IL-6 inhibition correlated positively with the TNF-α mRNA level in the primary tissue, but this was not significant. CONCLUSIONS: Imatinib mesylate can be expected to reduce inflammation and tissue remodelling in GO, while adalimumab can be mainly expected to reduce inflammation. This in vitro tissue-culture model may, in future, prove valuable to test novel therapeutics for their presumed effect in GO as well as in other inflammatory diseases.

Platelet-derived growth factor-BB: a stimulus for cytokine production by orbital fibroblasts in Graves' ophthalmopathy.

PURPOSE: Graves' ophthalmopathy (GO) is characterized by the infiltration of immune cells into the orbit, a process in which cytokines play a central role. Orbital fibroblasts are potent producers of cytokines on different stimuli. Recently, the authors showed increased expression of the PDGF-B chain in GO orbital tissue. The dimeric PDGF-BB molecule has been described to activate the NF-kappaB pathway, which is well recognized for its role in regulating cytokine production. This study was conducted to determine the role of PDGF-BB in the production of proinflammatory cytokines by orbital fibroblasts in GO. METHODS: Orbital, lung, and skin fibroblasts were stimulated with PDGF-BB, and cytokine (IL-1beta, IL-6, IL-8, IL-16, CCL2, CCL5, CCL7, TNF-alpha) production was measured by ELISA. Involvement of NF-kappaB activation through PDGF signaling was investigated by electrophoretic mobility shift assay, specific NF-kappaB inhibitors, and the PDGF-receptor kinase inhibitor imatinib mesylate. RESULTS: IL-6, IL-8, CCL2, CCL5, and CCL7 production by orbital fibroblasts was increased by PDGF-BB stimulation, whereas IL-16, IL-1beta, and TNF-alpha production was not affected. PDGF-BB induced NF-kappaB activity in orbital fibroblasts, and both NF-kappaB inhibitors and imatinib mesylate reduced PDGF-BB-induced cytokine production. Similar, but less vigorous, effects of PDGF-BB on cytokine production were observed in lung and skin fibroblasts. CONCLUSIONS: PDGF-BB is a potent inducer of proinflammatory cytokines via the NF-kappaB pathway in orbital fibroblasts, whereas cytokine production by fibroblasts from other anatomic locations showed a moderate response. These data suggest a possible role for PDGF-BB in regulating orbital inflammation in GO and identify the PDGF signaling cascade as a therapeutic target in GO.

Imatinib mesylate and AMN107 inhibit PDGF-signaling in orbital fibroblasts: a potential treatment for Graves' ophthalmopathy.

PURPOSE: Excessive orbital fibroblast proliferation and hyaluronan production are characteristic of Graves' ophthalmopathy (GO) and are driven by local mediators. Imatinib mesylate and AMN107 are tyrosine kinase inhibitors that inhibit fibroblast proliferation and collagen production in lungs and skin. This study was conducted to determine whether imatinib mesylate and AMN107 inhibit orbital fibroblast proliferation and hyaluronan production induced by PDGF-BB and TGF-beta(1) and whether expression of the genes PDGF-B and TGF-B(1) (growth factors suggested to play a role in GO) are increased in GO orbital tissues. METHODS: PDGF-B and TGF-B(1) mRNA levels were determined in orbital tissues of 13 patients with GO and 5 control patients. Orbital fibroblasts were cultured from eight patients with GO and three control patients and the effect of imatinib mesylate and AMN107 on PDGF-BB and TGF-beta(1)-induced orbital fibroblast proliferation, signaling cascades, hyaluronan synthase (HAS) gene expression and hyaluronan production were determined. RESULTS: PDGF-B and TGF-B(1) mRNA levels were significantly increased in GO orbital tissues. Imatinib mesylate and AMN107 inhibited PDGF-BB-induced orbital fibroblast proliferation, HAS induction and hyaluronan production by blocking PDGF-receptor phosphorylation. TGF-beta(1) induced HAS expression and hyaluronan production. This induction was not inhibited by imatinib mesylate or AMN107, due to the inability of TGF-beta(1) to activate c-Abl kinase activity in orbital fibroblasts. CONCLUSIONS: Imatinib mesylate and AMN107 inhibit orbital fibroblast proliferation and hyaluronan production induced by PDGF-BB; a factor highly expressed in orbital tissue from patients with GO. The drugs, however, had no effect on TGF-beta(1)-induced HAS expression and hyaluronan production. Nevertheless, imatinib mesylate and AMN107 should be considered as treatment candidates for GO.

Reconstruction following subtotal full-thickness upper eyelid resection with preservation of the lid margin.

PURPOSE: To describe a modification of a technique for upper eyelid reconstruction previously described by Patrinely et al. METHODS: Radical excision of a large adenoid cystic carcinoma of the upper eyelid resulted in a subtotal full-thickness eyelid defect with preservation of 2 mm of eyelid margin. Reconstruction was performed with a free transconjunctival graft of maximum size from the contralateral upper eyelid, an overlying bipedicled skin-orbicularis oculi muscle flap and a free skin graft. RESULTS: With this one-step technique, a good cosmetic and functional result could be obtained. CONCLUSION: If the eyelid margin can be spared, reconstruction of even very large upper eyelid defects with a modification of the technique reported by Patrinely et al. may yield a good result.