Synchronous vs. Metachronous Metastases in Adrenocortical Carcinoma: an Analysis of the Dutch Adrenal Network.

Adrenal Cortical Carcinoma (ACC) is a rare malignancy with an incidence of 1.0 per million per year in the Netherlands. Median survival varies according to the European Network for the Study of Adrenal Tumours (ENS@T) tumour stage. It is unknown whether time until development of metastases is of influence on prognosis. To asses this, data were retrospectively obtained from centres of the Dutch Adrenal Network. Patients who presented with ACC between January 1, 2004 and October 31, 2013 were included. Date of detection of metastases, number of metastases and affected organs were registered. One hundred sixty patients were included in the analysis. Synchronous metastases were defined as diagnosis of metastasis ≤6 months after the initial diagnosis of ACC. Overall survival rate was calculated from the date of diagnosis of metastasis until death from any cause. At first presentation, 50 patients (31 %) had ACC with metastases (ENS@T stage IV). Another 67 (42 %) developed metastases during follow-up. Amongst the 117 patients with metastases, 84 (72 %) patients had synchronous metastases and 33 (28 %) developed metachronous metastases. Diagnosis of synchronous metastases (p = 0.046), more than one affected organ (p < 0.001) and four or more metastases (p < 0.001) were found to be associated with reduced overall survival. Limitations included retrospective design and limited details regarding pathological data. We conclude that synchronous metastases of ACC are associated with a poorer prognosis compared to metachronous metastases of ACC. The clinical characteristics associated with prognosis in this study support the view to refine the prognostic classification for patients with stage IV ACC.

Retinal nerve fibre layer thickness measurement reproducibility improved with spectral domain optical coherence tomography.

BACKGROUND/AIMS: To investigate retinal nerve fibre layer (RNFL) thickness measurement reproducibility using conventional time-domain optical coherence tomography (TD-OCT) and spectral-domain OCT (SD-OCT), and to evaluate two methods defining the optic nerve head (ONH) centring: Centred Each Time (CET) vs Centred Once (CO), in terms of RNFL thickness measurement variability on SD-OCT. METHODS: Twenty-seven eyes (14 healthy subjects) had three circumpapillary scans with TD-OCT and three raster scans (three-dimensional or 3D image data) around ONH with SD-OCT. SD-OCT images were analysed in two ways: (1) CET: ONH centre was defined on each image separately and (2) CO: ONH centre was defined on one image and exported to other images after scan registration. After defining the ONH centre, a 3.4 mm diameter virtual circular OCT was resampled on SD-OCT images to mimic the conventional circumpapillary RNFL thickness measurements taken with TD-OCT. RESULTS: CET and CO showed statistically significantly better reproducibility than TD-OCT except for 11:00 with CET. CET and CO methods showed similar reproducibility. CONCLUSIONS: SD-OCT 3D cube data generally showed better RNFL measurement reproducibility than TD-OCT. The choice of ONH centring methods did not affect RNFL measurement reproducibility.

In vivo functional imaging of intrinsic scattering changes in the human retina with high-speed ultrahigh resolution OCT.

Non-invasive methods of probing retinal function are of interest for the early detection of retinal disease. While retinal function is traditionally directly measured with the electroretinogram (ERG), recently functional optical imaging of the retina has been demonstrated. In this manuscript, stimulus-induced, intrinsic optical scattering changes in the human retina are measured in vivo with high-speed, ultrahigh resolution optical coherence tomography (OCT) operating at 50,000 axial scans per second and ~3.3 micron axial resolution. A stimulus and measurement protocol that enables measurement of functional OCT retinal signals is described. OCT signal changes in the photoreceptors are demonstrated. Two distinct responses having different temporal and spatial properties are reported. These results are discussed in the context of optical intrinsic signals measured previously in the retina by fundus imaging and scanning laser ophthalmoscopy. Finally, challenges associated with in vivo functional retinal imaging in human subjects are discussed.

Intravitreal bevacizumab (Avastin) treatment of choroidal neovascularisation in patients with angioid streaks.

OBJECTIVE: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin) as treatment for choroidal neovascularisation (CNV) associated with angioid streaks METHODS: A non-randomised, interventional case series conducted on eyes with subfoveal CNV associated with angioid streaks. Intravitreal bevacizumab (1.25 mg in 0.05 ml) was injected into nine eyes of six patients between August 2005 and December 2007. Treatment efficacy was assessed based on pre- and post-treatment visual acuity and optical coherence tomography (OCT). RESULTS: With a mean follow-up of 19 months (range 10 to 28 months), the best corrected visual acuity improved by three or more lines in four eyes (44.4%), remained within two lines of baseline in four eyes (44.4%) and decreased by three or more lines in one eye (11.1%). Central foveal thickness (CFT) measured by OCT decreased an average of 67.7 microm (range +11 to -175 microm) with an average improvement in standardised change in macular thickening of 46.6% (range -12% to +84.5%). No injection-related complications or drug-related side effects were observed. CONCLUSIONS: Intravitreal bevacizumab for the treatment of subfoveal CNV secondary to angioid streaks mildly reduced central foveal thickness with a trend toward stabilisation of visual acuity. Additional follow-up and a larger patient cohort are needed to evaluate the long-term effects of this treatment.

Oxidative stress and antioxidant status in older adults with early cataract.

PURPOSE: Oxidative stress and antioxidant status were determined in forty healthy men and postmenopausal women aged 50-70 years (F25, M15), who underwent concurrent eye examinations. METHODS: Blood samples were collected for analysing major well-known antioxidants by HPLC systems with UV and ECD detectors, total antioxidant performance using a fluorometry, lipid peroxidation determined by malondialdehyde using a HPLC system with a fluorescent detector and by total hydroxyoctadecadienoic acid (HODE) and F2-isoprotanes (8-iso-PGF(2alpha)) using GC-MS. RESULTS: Twenty-seven (F17, M10) of the 40 subjects were diagnosed to have early cataracts at the onset of the study, which were regarded as age appropriate lens opacities. There was no significant difference in plasma major antioxidants, total antioxidant performance, and lipid peroxidation determined by malondialdehyde as well as 8-iso-PGF(2alpha) between the groups with and without early cataract. However, isomers of 9- and 13-(Z,E)-HODE levels were significantly higher in subjects with early cataract as compared with those of non-cataract subjects (P<0.05). CONCLUSION: Our data suggest that subjects with early cataract are under increased systemic oxidative stress, which can be identified by a sensitive biomarker of lipid peroxidation, such as isomers of HODE.

Projection OCT fundus imaging for visualising outer retinal pathology in non-exudative age-related macular degeneration.

AIMS: To demonstrate ultrahigh-resolution, three-dimensional optical coherence tomography (3D-OCT) and projection OCT fundus imaging for enhanced visualisation of outer retinal pathology in non-exudative age-related macular degeneration (AMD). METHODS: A high-speed, 3.5 mum resolution OCT prototype instrument was developed for the ophthalmic clinic. Eighty-three patients with non-exudative AMD were imaged. Projection OCT fundus images were generated from 3D-OCT data by selectively summing different retinal depth levels. Results were compared with standard ophthalmic examination, including fundus photography and fluorescein angiography, when indicated. RESULTS: Projection OCT fundus imaging enhanced the visualisation of outer retinal pathology in non-exudative AMD. Different types of drusen exhibited distinct features in projection OCT images. Photoreceptor disruption was indicated by loss of the photoreceptor inner/outer segment (IS/OS) boundary and external limiting membrane (ELM). RPE atrophy can be assessed using choroid-level projection OCT images. CONCLUSIONS: Projection OCT fundus imaging facilities rapid interpretation of large 3D-OCT data sets. Projection OCT enhances contrast and visualises outer retinal pathology not visible with standard fundus imaging or OCT fundus imaging. Projection OCT fundus images enable registration with standard ophthalmic diagnostics and cross-sectional OCT images. Outer retinal alterations can be assessed and drusen morphology, photoreceptor impairment and pigmentary abnormalities identified.

In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography.

Noninvasive in vivo functional optical imaging of the intact retina is demonstrated by using high-speed, ultrahigh-resolution optical coherence tomography (OCT). Imaging was performed with 2.8 microm resolution at a rate of 24,000 axial scans per second. A white-light stimulus was applied to the dark-adapted rat retina, and the average reflectivities from different intraretinal layers were monitored as a function of time. A 10%-15% increase in the average amplitude reflectance of the photoreceptor outer segments was observed in response to the stimulus. The spatial distribution of the change in the OCT signal is consistent with an increase in backscatter from the photoreceptor outer segments. To our knowledge, this is the first in vivo demonstration of OCT functional imaging in the intact retina.

Ultrahigh resolution optical coherence tomography in non-exudative age related macular degeneration.

AIM: To describe the appearance of the non-exudative forms of age related macular degeneration (AMD) as imaged by ultrahigh resolution optical coherence tomography (UHR-OCT). METHODS: A UHR-OCT ophthalmic imaging system, which utilises a femtosecond laser light source capable of approximately 3 mum axial resolution, was employed to obtain retinal cross sectional images of patients with non-exudative AMD. Observational studies of the resulting retinal images were performed. RESULTS: 52 eyes of 42 patients with the clinical diagnosis of non-exudative AMD were imaged using the UHR-OCT system. 47 of the 52 (90%) eyes had the clinical diagnosis of drusen and/or retinal pigment epithelial (RPE) changes. In these patients, three patterns of drusen were apparent on UHR-OCT: (1) distinct RPE excrescences, (2) a saw toothed pattern of the RPE, and (3) nodular drusen. On UHR-OCT, three eyes (6%) with a clinical diagnosis of non-exudative AMD had evidence of fluid under the retina or RPE. Two of these three patients had findings suspicious for subclinical choroidal neovascularisation on UHR-OCT. CONCLUSION: With the increased resolution of UHR-OCT compared to standard OCT, the involvement of the outer retinal layers are more clearly defined. UHR-OCT may allow for the detection of early exudative changes not visible clinically or by angiography.

Evaluation of swallowing function after intraoral soft tissue reconstruction with microvascular free flaps.

This study assessed swallowing function after tumour resection and reconstruction utilizing free vascularized flap closures in patients with oral cancer. Swallowing function was evaluated postoperatively in 23 patients (21 men and 2 women) who had undergone reconstruction with either a lateral upper arm free flap (LUFF, n=16) or a radial forearm free flap (RFFF, n=7). Videofluoroscopy was used to assess tongue mobility and abnormalities of swallowing function. All patients who underwent reconstruction with LUFF or RFFF free flaps had decreased tongue mobility, except for the tip of the tongue. Patients who underwent anterior or posterior resection had greater decreases in tongue mobility than those who underwent medial resection. Swallowing impairment was similar in patients with LUFFs and those with RFFFs. Anterior resection of the oral cavity had a significant negative effect on swallowing function. Silent aspiration occurred in five patients. In conclusion the resection site affected swallowing function, but the type of flap did not, in patients with oral carcinoma, who underwent tumour resection with reconstruction

Swallowing and speech function after intraoral soft tissue reconstruction with lateral upper arm free flap and radial forearm free flap.

Swallowing, speech, and morbidity were assessed postoperatively in 25 patients, 18 of whom had had intraoral defects reconstructed by lateral upper arm free flaps (LUFF) and 7 by radial forearm free flaps (RFFF). Video fluoroscopy was used to assess swallowing, the Freiburger audiometric test to assess speech; and measurement of arm circumference to assess donor site morbidity. A questionnaire was used to evaluate swallowing, speech, and donor site morbidity subjectively. The degree of impairment in swallowing depended on the site of resection. Anterior and posterior resections affected swallowing more than lateral resections. Anterior resection and the use of LUFFs reduced intelligibility. There was no significant difference in impairment between LUFF and RFFF. We conclude that the LUFFs are superior to RFFFs because they can be closed primary and the incidence of donor site morbidity is slight.

[Color duplex ultrasound in monitoring vascularized fibula transplants]. / Farbduplexsonographie zum Monitoring von vaskularisierten Fibulatransplantaten.

BACKGROUND: For the successful management of vascularized free fibular bone grafts, the early detection of vascular complications is important. When vascular complications are suspected without a reliable monitoring of the graft perfusion, revision surgery often proved to be unnecessary. Color duplex sonography for the postoperative monitoring of free fibular bone grafts without a skin island is demonstrated. MATERIAL AND METHODS: The quantitative and qualitative monitoring of the perfusion of microvascular anastomosis and the transplanted tissues using color duplex sonography with a 7.5-Mhz scanner (Elegra, Siemens, Germany) for the postoperative monitoring of 12 free fibular bone grafts was performed. Using color duplex sonography, the perfusion of the vascular pedicle and the free fibular bone grafts was demonstrated in all 12 free fibular bone grafts. In three patients vascular complications and failure of the bone grafts were suspected due to postoperative complications next to free fibular bone grafts such as abscess formation, wound dehiscence, and disturbances of wound healing. Using color duplex sonography, adequate perfusion of the vascular pedicle and the transplanted tissue was demonstrated and therefore revision surgery not indicated. DISCUSSION: Color duplex sonography is a reliable, noninvasive, and inexpensive method for the postoperative monitoring of free fibular bone grafts.

Versatility and donor site morbidity of the lateral upper arm flap in intraoral reconstruction.

OBJECTIVE: The lateral upper arm flap is not widely used yet for intraoral defect reconstruction. Investigation of its morphologic and functional outcome was the objective of this study. STUDY DESIGN: The morphologic and functional results of recipient (swallowing, flap survival, dehiscence of margins, cutaneous fistulas, intraoral hairs) and donor sites (wound healing, scar width and length, sensory and motor disturbance) (n = 44) were checked clinically. Postoperative swallowing was investigated via videofluorography (n = 11). RESULTS: The lateral upper arm flap showed low donor site morbidity, primary closure was achieved in all but one case. Sensory deficit at the proximal forearm (n = 27) occurred without any case of compromise of radial nerve function. Videofluorography allows for objective evaluation of swallowing function. CONCLUSIONS: The lateral upper arm flap is the reconstruction of first choice for intraoral defects due to its low donor site morbidity.

Transpupillary thermotherapy (TTT) of occult choroidal neovascularization: a retrospective, noncomparative case series of fifty-seven eyes.

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) for the treatment of occult choroidal neovascularization. METHODS: A retrospective, noncomparative case series of 57 eyes of 52 patients who presented with occult subfoveal CNV and were treated with TTT. RESULTS: 83% of eyes were either stable (+/- one line) or showed improvement in visual acuity. 83% of eyes showed stabilization of their exudative process after one TTT treatment as evidenced by resorption of subretinal and/or intraretinal exudate or hemorrhage. Nine percent of eyes developed classic CNV during the mean follow-up time of ten months. CONCLUSIONS: TTT appears to stabilize the exudative process in eyes with occult CNV. A prospective, sham-controlled, randomized study (TTT4CNV Clinical Trial) is currently underway to directly compare TTT to the natural history of occult CNV.

Endophthalmitis after pediatric strabismus surgery.

OBJECTIVE: To report 6 cases of endophthalmitis after pediatric strabismus surgery. METHODS: Retrospective review of initial signs, clinical findings, treatment, culture results, and visual and anatomical outcomes in 6 eyes of 6 children treated at 2 tertiary care institutions between 1983 and 1998. RESULTS: Four boys and 2 girls aged 8 months to 6 years (median age, 2 years) developed lethargy and asymmetric eye redness, with or without eyelid swelling or fever, within 4 days of surgery. At diagnosis (median, postoperative day 6) clinical findings included periorbital swelling, redness and leukocoria due to vitritis, and, in some cases, hypopyon. Treatment included pars plana vitrectomy and intravitreal and systemic antibiotics in all cases. Vitreous cultures grew Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Within 6 months of strabismus surgery, visual acuity was no light perception in all eyes and 3 eyes had been enucleated. The 3 remaining eyes were prephthisical. CONCLUSIONS: Endophthalmitis after pediatric strabismus surgery is rare. Children may not recognize or verbalize symptoms. Causative organisms are virulent. Visual and anatomical outcomes are poor. Lethargy, asymmetric eye redness, eyelid swelling, or fever in the postoperative period, even if initial postoperative examination results are normal, should prompt urgent ocular examination. The diagnosis of endophthalmitis may be made when biomicroscopic or indirect ophthalmoscopic examination confirms the presence of vitreous opacification with or without hypopyon. Arch Ophthalmol. 2000;118:939-944

Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration.

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy for the treatment of occult subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration. DESIGN: A retrospective, noncomparative case series. PARTICIPANTS: Sixteen eyes of 15 consecutive patients who presented with occult subfoveal choroidal neovascularization secondary to age-related macular degeneration. INTERVENTION: After informed consent was obtained, 16 eyes of 15 patients were treated with transpupillary thermotherapy. All patients underwent pretreatment fluorescein angiography and were deemed untreatable by the Macular Photocoagulation Study standard. Transpupillary thermotherapy was delivered using a diode laser at 810 nm. A variable spot size of 1.2 mm, 2.0 mm, or 3.0 mm was used depending on the size of CNV. The diode laser was delivered through a contact lens, and treatment was initiated in one spot for 60 seconds' duration at a power range between 360 and 1000 mW. The end point was an area of no visible color change to a light-gray appearance. MAIN OUTCOME MEASURES: In all eyes, outcome was assessed by Snellen chart visual acuity and clinical examination. In 10 of 16 eyes, preoperative and postoperative fluorescein angiography and optical coherence tomography were available. In the remaining 6 of 16 eyes, exudation was measured by postoperative clinical examination alone. RESULTS: Three eyes (19%) showed a two-or-more-line improvement in visual acuity over a period of 6 to 25 months. Mean follow-up was 13 months. Visual acuity remained stable (no change or one-line improvement) in nine treated eyes (56%). The remaining four eyes (25%) showed a decline (equal to one-line worsening or greater) in visual acuity. Fifteen eyes (94%) demonstrated decreased exudation on fluorescein angiography, optical coherence tomography, and/or clinical examination. CONCLUSIONS: Transpupillary thermotherapy shows no deleterious side effects in treating occult subfoveal choroidal neovascularization. A randomized, prospective study is necessary to evaluate treatment efficacy.