Vitreoretinal surgical performance after acute alcohol consumption and hangover.

AIM: Routine alcohol testing of practicing physicians remains controversial since there are no uniform guidelines or legal regulations in the medical field. Our aim was to quantitatively study the acute and next-morning effects of breath alcohol concentration (BAC)-adjusted alcohol intake on overall simulated surgical performance and microtremor among senior vitreoretinal surgeons. METHODS: This prospective cohort study included 11 vitreoretinal surgeons (>10 years practice). Surgical performance was first assessed using the Eyesi surgical simulator following same-day alcohol consumption producing a BAC reading of 0.06%-0.10% (low-dose), followed by 0.11%-0.15% (high-dose). Dexterity was then evaluated after a 'night out' producing a high-dose BAC combined with a night's sleep. Changes in the total score (0-700, worst-best) and tremor (0-100, best-worst) were measured. RESULTS: Surgeon performance declined after high-dose alcohol compared with low-dose alcohol (-8.60±10.77 vs -1.21±7.71, p=0.04, respectively). The performance during hangover was similar to low-dose alcohol (-1.76±14.47 vs -1.21±7.71, p=1.00, respectively). The performance during hangover tended to be better than after high-dose alcohol (-1.76±14.47 vs -8.60±10.77, p=0.09, respectively). Tremor increased during hangover compared with low-dose alcohol (7.33±21.65 vs -10.31±10.73, p=0.03, respectively). A trend toward greater tremor during hangover occurred compared with high-dose alcohol (7.33±21.65 vs -4.12±17.17, p=0.08, respectively). CONCLUSION: Alcohol-related decline in simulated surgical dexterity among senior vitreoretinal surgeons was dose-dependent. Dexterity improved the following morning but remained comparable to after low-dose alcohol ingestion. Tremor increased during hangover compared with same-day intoxication. Further studies are needed to investigate extrapolations of these data to a real surgical environment regarding patient safety and surgeon performance.

ASSESSMENT OF SIMULATED SURGICAL DEXTERITY AFTER MODIFIABLE EXTERNAL EXPOSURES AMONG NOVICE VERSUS EXPERIENCED VITREORETINAL SURGEONS.

PURPOSE: To evaluate novice and senior vitreoretinal surgeons after various exposures. Multiple comparisons ranked the importance of these exposures for surgical dexterity based on experience. METHODS: This prospective cohort study included 15 novice and 11 senior vitreoretinal surgeons (<2 and >10 years' practice, respectively). Eyesi-simulator tasks were performed after each exposure. Day 1, placebo, 2.5 mg/kg caffeine, and 5.0 mg/kg caffeine; day 2, placebo, 0.2 mg/kg propranolol, and 0.6 mg/kg propranolol; day 3, baseline simulation, breathalyzer readings of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentrations; day 4, baseline simulation, push-up sets with 50% and 85% repetitions maximum; and day 5, 3-hour sleep deprivation. Eyesi-generated score (0-700, worst-best), out-of-tolerance tremor (0-100, best-worst), task completion time (minutes), and intraocular pathway (in millimeters) were measured. RESULTS: Novice surgeons performed worse after caffeine (-29.53, 95% confidence interval [CI]: -57.80 to -1.27, P = 0.041) and alcohol (-51.33, 95% CI: -80.49 to -22.16, P = 0.001) consumption. Alcohol caused longer intraocular instrument movement pathways (212.84 mm, 95% CI: 34.03-391.65 mm, P = 0.02) and greater tremor (7.72, 95% CI: 0.74-14.70, P = 0.003) among novices. Sleep deprivation negatively affected novice performance time (2.57 minutes, 95% CI: 1.09-4.05 minutes, P = 0.001) and tremor (8.62, 95% CI: 0.80-16.45, P = 0.03); however, their speed increased after propranolol (-1.43 minutes, 95% CI: -2.71 to -0.15 minutes, P = 0.029). Senior surgeons' scores deteriorated only following alcohol consumption (-47.36, 95% CI: -80.37 to -14.36, P = 0.005). CONCLUSION: Alcohol compromised all participants despite their expertise level. Experience negated the effects of caffeine, propranolol, exercise, and sleep deprivation on surgical skills.

A Polysomnographic Study of Effects of Sleep Deprivation on Novice and Senior Surgeons during Simulated Vitreoretinal Surgery.

PURPOSE: To assess the impact of a 3-hour polysomnography (PSG)-recorded night of sleep deprivation on next-morning simulated microsurgical skills among vitreoretinal (VR) surgeons with different levels of surgical experience and associate the sleep parameters obtained by PSG with Eyesi-generated performance. DESIGN: Self-controlled cohort study. PARTICIPANTS: Eleven junior VR surgery fellows with < 2 years of surgical experience and 11 senior surgeons with > 10 years of surgical practice. METHODS: Surgical performance was assessed at 7am after a 3-hour sleep-deprived night using the Eyesi simulator and compared with each subject's baseline performance. MAIN OUTCOME MEASURES: Changes in Eyesi-generated score (0-700, worst to best), time for task completion (minutes), tremor-specific score (0-100, worst to best), and out-of-tolerance tremor percentage. Polysomnography was recorded during sleep deprivation. RESULTS: Novice surgeons had worse simulated surgical performance after sleep deprivation compared with self-controlled baseline dexterity in the total score (559.1 ± 39.3 vs. 593.8 ± 31.7; P = 0.041), time for task completion (13.59 ± 3.87 minutes vs. 10.96 ± 1.95 minutes; P = 0.027), tremor-specific score (53.8 ± 19.7 vs. 70.0 ± 15.3; P = 0.031), and out-of-tolerance tremor (37.7% ± 11.9% vs. 28.0% ± 9.2%; P = 0.031), whereas no performance differences were detected in those parameters among the senior surgeons before and after sleep deprivation (P ≥ 0.05). Time for task completion increased by 26% (P = 0.048) in the post-sleep deprivation simulation sessions for all participants with a high apnea-hypopnea index (AHI) and by 37% (P = 0.008) among surgeons with fragmented sleep compared with those with normal AHI and < 10 arousals per hour, respectively. Fragmented sleep was the only polysomnographic parameter associated with a worse Eyesi-generated score, with a 10% (P = 0.005) decrease the following morning. CONCLUSIONS: This study detected impaired simulated surgical dexterity among novice surgeons after acute sleep deprivation, whereas senior surgeons maintained their surgical performance, suggesting that the impact of poor sleep quality on surgical skills is offset by increased experience. When considering the 2 study groups together, sleep fragmentation and AHI were associated with jeopardized surgical performance after sleep deprivation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Weight-adjusted caffeine and ß-blocker use in novice versus senior retina surgeons: a self-controlled study of simulated performance.

BACKGROUND/OBJECTIVES: Tremor and expertise are potentially influenced variables in vitreoretinal surgery. We investigated whether surgeon experience impacts the association of microsurgical performance with caffeine and ß-blockers weight-adjusted intake. SUBJECTS/METHODS: Novice and senior surgeons (<2 and >10 practice years, respectively) were recruited in this self-controlled, cross-sectional study. A simulator's task sequence was repeated over 2 days, 30 min after the following exposures: day 1, placebo, 2.5 mg/kg caffeine, 5.0 mg/kg caffeine, and 0.6 mg/kg propranolol; and day 2, placebo, 0.2 mg/kg propranolol, 0.6 mg/kg propranolol, and 5.0 mg/kg caffeine. Outcomes were total score (0-700, worst-best), simulation time (minutes), intraocular trajectory (centimeters), and tremor-specific score (0-100, worst-best). RESULTS: We recruited 15 novices (9 men [60%], 1.33 ± 0.49 practice years) and 11 seniors (8 men [72.7%], 16.00 ± 4.24 practice years). Novices performed worse after 2.5 mg/kg caffeine and improved following 0.2 mg/kg propranolol in total score (557 vs. 617, p = 0.009), trajectory (229.86 vs. 208.07, p = 0.048), time (14.9 vs. 12.7, p = 0.048), and tremor-score (55 vs. 75, p = 0.009). Surgical performance improved with propranolol post-caffeine but remained worse than 0.2 mg/kg propranolol in total score (570 vs. 617, p = 0.014), trajectory (226.59 vs. 208.07, p = 0.033), and tremor-score (50 vs. 75, p = 0.029). Seniors' tremor-score was lower after 2.5 mg/kg caffeine compared to 0.2 mg/kg propranolol (8 vs. 37, p = 0.015). Tremor-score following propranolol post-caffeine remained inferior to 0.6 mg/kg propranolol alone (17 vs. 38, p = 0.012). CONCLUSION: While caffeine and propranolol were associated with performance changes among novices, only tremor was affected in seniors, without dexterity changes. The pharmacologic exposure impact on surgical dexterity seems to be offset by increased experience.

Impact of manual correction over automated segmentation of spectral domain optical coherence tomography.

OBJECTIVE: To study the automated segmentation of retinal layers using spectral domain optical coherence tomography (OCT) and the impact of manual correction over segmentation mistakes. METHODS: This was a retrospective, cross-sectional, comparative study that compared the automated segmentation of macular thickness using Spectralis™ OCT technology (Heidelberg Engineering, Heidelberg, Germany) versus manual segmentation in eyes with no macular changes, macular cystoid edema (CME), and choroidal neovascularization (CNV). Automated segmentation of macular thickness was manually corrected by two independent examiners and reanalyzed by them together in case of disagreement. RESULTS: In total, 306 eyes of 254 consecutive patients were evaluated. No statistically significant differences were noted between automated and manual macular thickness measurements in patients with normal maculas, while a statistically significant difference was found in central thickness in patients with CNV and with CME. Segmentation mistakes in macular OCTs were present in 5.3% (5 of 95) in the normal macula group, 16.4% (23 of 140) in the CME group, and 66.2% (47 of 71) in CNV group. The difference between automated and manual macular thickness was higher than 10% in 1.4% (2 of 140) in the CME group and in 28.17% (20 of 71) in the CNV group. Only one case in the normal group had a higher than 10% segmentation error (1 of 95). CONCLUSION: The evaluation of automated segmented OCT images revealed appropriate delimitation of macular thickness in patients with no macular changes or with CME, since the frequency and magnitude of the segmentation mistakes had low impact over clinical evaluation of the images. Conversely, automated macular thickness segmentation in patients with CNV showed a high frequency and magnitude of mistakes, with potential impact on clinical analysis.

CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH RETINAL PIGMENT EPITHELIAL TEAR IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To report a patient presenting a retinal pigment epithelial tear in which optical coherence tomography angiography enabled the visualization of subfoveal choroidal neovascularization (CNV) not evidenced by the fluorescein angiography. She was treated with 3 monthly intravitreous anti-VEGF injections and intraretinal fluid resolution occurred. METHODS: Observational case report. RESULTS: A 62-year-old Caucasian woman presented with decreased visual acuity in the right eye for 3 months. Fundus biomicroscopy revealed a yellowish macular lesion associated with intraretinal hemorrhage. Fluorescein angiography showed a large hyperfluorescent area consistent with window defect. Optical coherence tomography showed a retinal pigment epithelial tear with subretinal fluid. However, there was no clear evidence of CNV on fluorescein angiography or OCT. Optical coherence tomography angiography confirmed the presence of an active CNV by the visualization of the neovascular network in the region corresponding to the scrolled up retinal pigment epithelium. CONCLUSION: This case report demonstrates that optical coherence tomography angiography can be useful to confirm the presence of CNV in cases where fluorescein angiography and OCT cannot establish the diagnosis. The reported case suggests the applicability of optical coherence tomography angiography in patients in whom retinal pigment epithelial tear is detected and associated CNV is suspected.

Optical coherence tomography angiography artifactual choroidal neovascularization in optic disc pit maculopathy.

This case report describes a 19-year-old Caucasian man presented with decreased visual acuity in the right eye for 3 months. Dilated funds exam revealed optic disk pit associated with serous macular detachment. Optical coherence tomography identified communication between the optic disk pit and the macular serous detachment, and optical coherence tomography angiography displayed a subfoveal area suggestive of subfoveal choroidal neovascularization. However, there was no evidence of leakage in the fluorescein angiogram and no evidence of choroidal neovascularization in optical coherence tomography in the area corresponding to the suspicious subfoveal choroidal neovascularization. The patient underwent 23-gauge pars plana vitrectomy in the right eye. Six weeks after surgery, multimodal imaging was repeated and there was near-complete resorption of the subretinal fluid. Optical coherence tomography angiography signal superimposed on optical coherence tomography B-scan also demonstrated normal choriocapillaris signal throughout the macula. In conclusion, optical coherence tomography angiography may produce artifacts in optic disk pit maculopathy that simulate choroidal neovascularization.

Optical coherence tomography angiography artifactual choroidal neovascularization in optic disc pit maculopathy / Artefato de neovascularização de coroide na angiografia por tomografia de coerência óptica em pit de disco óptico

ABSTRACT This case report describes a 19-year-old Caucasian man presented with decreased visual acuity in the right eye for 3 months. Dilated funds exam revealed optic disk pit associated with serous macular detachment. Optical coherence tomography identified communication between the optic disk pit and the macular serous detachment, and optical coherence tomography angiography displayed a subfoveal area suggestive of subfoveal choroidal neovascularization. However, there was no evidence of leakage in the fluorescein angiogram and no evidence of choroidal neovascularization in optical coherence tomography in the area corresponding to the suspicious subfoveal choroidal neovascularization. The patient underwent 23-gauge pars plana vitrectomy in the right eye. Six weeks after surgery, multimodal imaging was repeated and there was near-complete resorption of the subretinal fluid. Optical coherence tomography angiography signal superimposed on optical coherence tomography B-scan also demonstrated normal choriocapillaris signal throughout the macula. In conclusion, optical coherence tomography angiography may produce artifacts in optic disk pit maculopathy that simulate choroidal neovascularization.

RESUMO O presente estudo relatou o caso de um homem caucasiano de 19 anos com diminuição da acuidade visual no olho direito há 3 meses. Na fundoscopia havia um pit de papila associado ao descolamento seroso macular. A tomografia de coerência óptica identificou uma comunicação entre o pit e o descolamento seroso e a angiografia por tomografia de coerência óptica demonstrou uma área subfoveal sugestiva de membrana neovascular sub-retiniana. No entanto, não houve evidência de vazamento na angiofluoresceínografia com contraste e nem de membrana neovascular sub-retiniana na tomografia de coerência óptica na área suspeita. O paciente foi submetido a vitrectomia pars plana 23-gauge no olho direito. Seis semanas após a cirurgia, os exames foram repetidos e houve reabsorção quase completa do líquido sub-retiniano. O sinal da angiografia por tomografia de coerência óptica sobreposto à tomografia de coerência óptica B-scan era normal na região da mácula. Em conclusão, a angiografia por tomografia de coerência óptica pode produzir artefatos em maculopatia secundária a pit de papila que simulam uma membrana neovascular sub-retiniana.

Avaliação da eficácia de um novo marcador cirúrgico para capsulorrexe anterior / Effectiveness evaluation of a new surgical marker for anterior capsulorhexis

RESUMO Objetivo: Avaliar a eficácia de um novo marcador cirúrgico para ajudar na confecção da capsulorrexe anterior analisando o seu dimensionamento e formato, comparando com a capsulorrexe confeccionada manualmente de maneira livre. Métodos: Como experimento, 3 residentes (R3) de Oftalmologia do Hospital Universitário Onofre Lopes (HUOL) e 1 oftalmologista em treinamento, voluntários, realizaram (cada um) 10 capsulorrexes em olhos de porco enucleados. Em 5 olhos foi utilizado o marcador e em outros 5, não. Todos os olhos foram fotografados tendo ao lado uma régua para orientar e calibrar um aplicativo para a avaliação morfométrica do procedimento. O diâmetro alvo foi de 5 mm, cujo perímetro correspondente é 15,7 mm e a área 19,652 mm2. Foram avaliados em cada procedimento: os diâmetros máximo, mínimo e médio, o perímetro, a área e o desvio em relação ao diâmetro e quanto ao aspecto ideal. Resultados: No grupo utilizando o marcador o diâmetro médio foi 5,44mm (±0,89) contra 6,37mm (±0,67) (p=0,001), no grupo no qual não se utilizou o marcador; quanto ao perímetro, 17,52mm (±1,92) no grupo utilizando o marcador contra 20,14mm (±2,09) (p<0,001) sem o marcador e quanto a área, 24,73mm2 (±1,92) com o marcador, contra 32,62mm2 (±6,32) (p<0,001), sem o marcador. Em relação ao aspecto da capsulorrexe 1,26mm (±0,12), contra 1,21mm (±0,7) (p=0,09) e em relação ao desvio de curvatura: 0,87 (±0,05), contra 0,9 (±0,04), (p=0,06) respectivamente. Conclusão: O trabalho mostrou que o marcador avaliado é eficaz para auxiliar a confecção da capsulorrexe conduzindo a resultados melhores que o método a mão livre.

ABSTRACT Purpose: To evaluate the effectiveness of a surgical device that intented to help in the preparation of the anterior capsulorhexis analyzing the design and shape, comparing with capsulorhexis made by free hand. Methods: Three ophthalmology residents(R3) at the HUOL and one surgeon in training, participate in this research as volunteers. Each surgeon perform 5 capsulorhexis in porcine eyes using the device, and five others by free hand as a control. All capsulorhexis were photographed having a ruler as reference to guide and calibrate a computer application for morphometric evaluation (Cambuí Labs, Natal, Brazil). All surgeons aimed to produce a circular continuous capsulorhexis of 5 mm diameter that represents 15,7mm in perimeter and 19,652mm2 in area. Each wet-lab capsulorhexis was evaluated in regard to these criteria: diameter (mean, maximum and minimum), perimeter, area, deviation from the ideal diameter and ideal shape. Results: Compare to control groups, capsulorhexis with the aid of the surgical device showed: 5,44mm ±0,89 vs 6,37mm ±0,67, for capsulorhexis diameter (p=0,001); 17,52mm ±1,92 vs 20,14mm ±2,09 for capsulorhexis perimeter (<0.001); 24,73mm2 ±1,92 vs 32,62mm2 ±6,36 for capsulorhexis area (p<0,001). A tendency for better result with the aid of the surgical device was observed for deviation of an ideal diameter or ideal aspect were appreciated: 0,87mm ±0,05 vs 0,9 ±0,04 for deviation of a curve (p=0,06); 1,26mm ±0,12 vs 1,21mm ±0,7 for the capsulorhexis aspect (p=0,09). Conclusion: Capsulorhexis produced with the aid of the surgical device, significantly improved wet-lab capsulorhexis performance.

Acute retinal necrosis and immune reconstitution inflammatory syndrome in a natalizumab-treated patient with multiple sclerosis.

PURPOSE: To describe a case of acute retinal necrosis and subsequent immune reconstitution inflammatory syndrome in a patient with multiple sclerosis treated with natalizumab. METHODS: Case report. RESULTS: A 51-year-old man with multiple sclerosis developed acute retinal necrosis during treatment with natalizumab. The patient was successfully managed with natalizumab discontinuation, oral valacyclovir, and prophylactic laser retinal photocoagulation. A few months after natalizumab interruption and 1 month after valacyclovir completion, the patient presented with an episode of presumed noninfectious anterior and intermediate uveitis, which responded well to oral steroid mini-pulse therapy. CONCLUSION: Natalizumab is a potent immune suppressor used in the treatment of multiple sclerosis and Crohn disease. It has already been linked to herpetic infections and immune reconstitution inflammatory syndrome in the central nervous system. These complications may also affect ocular tissues.

Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma.

BACKGROUND: Melan-A and tyrosinase are new immunohistochemical markers that can be used in the diagnosis of melanocytic lesions. The aim of this study was to investigate the correlation between radiotherapy or clinicohistopathological parameters and the expression of melan-A and tyrosinase in uveal melanoma. METHODS: Thirty-six enucleated cases of uveal melanoma were studied. The formalin-fixed, paraffin-embedded specimens were immunostained with monoclonal antibodies against melan-A and tyrosinase. The samples were classified as either positive or negative. The chi-square or the Student-t tests were used to test for the correlation of the expression rates of melan-A and tyrosinase with clinico-pathological parameters. RESULTS: Melan-A and tyrosinase were positive in 33 (91.7%) and 35 (97.2%) of the specimens, respectively. There was no significant association between the expression of melan-A or tyrosinase and radiotherapy or any clinico-pathological parameter. All specimens were positive for at least one of the immunohistochemical markers. CONCLUSION: To the best of our knowledge this is the first study concluding that the expression of melanocytic markers such as melan-A and tyrosinase is not influenced by radiotherapy or any clinico-pathological parameter. Moreover, when tyrosinase and melan-A are used together, 100% of the formalin-fixed, paraffin-embedded uveal melanoma samples tested positive for one of those markers.

A case of anterior internal ophthalmomyiasis: case report.

A case of anterior internal ophthalmomyiasis is described. A 27-year-old female from Northern Brazil presenting with anterior uveitis and vitritis had a fly larva surgically removed from the anterior chamber of the left eye. The species was Cochliomyia hominivorax. The larva was covered by macrophages and foreign body giant cells characterizing a foreign body granulomatous reaction.

Malignancy in the blind painful eye--report of two cases and literature review.

BACKGROUND: Few cases of malignant tumors arising in a blind painful eye have previously been described. We described two cases of a blind painful eye containing an unsuspected tumor, which were enucleated to relieve the pain. CASE PRESENTATIONS: Case 1: A 57 year-old Caucasian man presented with recurrent orbital cellulitis and endophthalmitis in the left eye (OS). The OS was blind and painful and an enucleation was performed showing a uveal melanoma by histopathological exam. Case 2: A 54 year-old Caucasian man with previous history of a rhegmatogenous retinal detachment in his left eye presented a blind painful eye. Enucleation was performed revealing a well-differentiated B-cell lymphoma of uveal tract with extra ocular extension. CONCLUSION: In the management of a blind painful eye, it is extremely important to rule out an intraocular malignancy particularly in those patients who have not been followed by an ophthalmologist.

A case of anterior internal ophthalmomyiasis: case report / Oftalmomiíase interna anterior: relato de caso

A case of anterior internal ophthalmomyiasis is described. A 27-year-old female from Northern Brazil presenting with anterior uveitis and vitritis had a fly larva surgically removed from the anterior chamber of the left eye. The species was Cochliomyia hominivorax. The larva was covered by macrophages and foreign body giant cells characterizing a foreign body granulomatous reaction.

Um caso de oftalmomiíase interna anterior é descrito. Uma mulher de 27 anos proveniente da região Norte do Brasil com uveíte anterior e vitreíte teve uma larva de mosca cirurgicamente removida da câmara anterior do olho esquerdo. A espécie identificada foi Cochliomyia hominivorax. A larva estava coberta por macrófagos e células gigantes de corpo estranho, caracterizando uma reação granulomatosa de corpo estranho.

Basal cell carcinoma of the caruncle.

An 82-year-old white man presented with a 2- to 3-month history of a lesion in his left medial canthal region. Surgical excision of the lesion was performed, and histopathology showed a nodular basal cell carcinoma of the caruncle. Because of incomplete surgical margins after the initial excision, a second excision was performed, followed by a course of adjuvant radiotherapy. No tumor recurrence was detected in the caruncle after 6 months of follow-up.

Characterization of ocular and metastatic uveal melanoma in an animal model.

PURPOSE: To characterize, in detail, tumor development, malignant cell dissemination, and metastasis in a 10-week animal model of uveal melanoma. METHODS: One million 92.1 human primary uveal melanoma cells were injected into the suprachoroidal space of the right eye of 27 immunosuppressed albino rabbits. Intraocular tumor growth was monitored weekly by fundoscopy and by ultrasonography at the end of the experiment. To document the progression of the disease, one animal per week was killed. The enucleated eyes, lungs, and livers were macroscopically examined and histopathologically studied by hematoxylin and eosin, periodic acid-Schiff, and immunohistochemistry. Mononuclear layers isolated from the rabbits' blood samples were cultured. RESULTS: Histopathology showed intraocular tumors in 89% of the animals. Tumor growth was found 1 week after cell inoculation, and by the end of the experiment large tumor masses were observed. Microscopic pulmonary metastatic foci were first observed 4 weeks after cell injection. By the end of the experiment, all the animals had metastasis to the lungs. Interestingly, 18% of the animals also had micrometastasis to the liver. Viable adherent uveal melanoma cells were successfully isolated from peripheral blood and grown in vitro. CONCLUSIONS: In this study, most rabbits developed intraocular tumors followed by lung metastasis, and some of these rabbits later developed liver micrometastases. This novel source of research material warrants a follow-up longer than 10 weeks to further explore the pathophysiologic bases of liver involvement commonly encountered in humans. The success in the isolation and culture of circulating malignant cells in this animal model suggests that it might be worthwhile to explore the application of this technique to the management of patients with primary uveal melanoma.

Immunohistochemical expression of phospho-Akt in uveal melanoma.

The aim of this study was to evaluate the immunohistochemical expression of phospho-Akt and its possible association with clinicopathological features in uveal melanoma. Thirty-four enucleated eyes from 34 patients with choroidal melanoma were included in the study. Patients were divided into two groups based on the treatment received: (1) primary enucleation (n=18); (2) radiotherapy, either external beam or brachytherapy, and enucleation (n=16). Clinicopathological data were obtained. The minimum follow-up time was 72 months. Immunohistochemistry for phospho-Akt was performed using an anti-phospho-Akt (Ser 473) rabbit antibody. The association of phospho-Akt with clinicopathological parameters was investigated in each patient group separately. Phospho-Akt immunostaining was cytoplasmic in both groups. In the primary enucleation group, 10 tumours were phospho-Akt positive (55.5%). Patients with phospho-Akt-positive tumours were older (average 70.8 years versus 59 years, P=0.01) and phospho-Akt immunoreactivity was significantly associated with a higher risk of metastatic disease (Kaplan-Meier analysis, P=0.02). In the radiotherapy and enucleation group, nine tumours were phospho-Akt positive (56.2%). The absence of phospho-Akt expression was correlated with male gender (P=0.02). The following conclusions can be drawn from this study: (1) phospho-Akt immunoexpression was detected in 55.5% of uveal melanomas treated with primary enucleation and in 56.2% of uveal melanomas treated with radiotherapy and enucleation; (2) the association of phospho-Akt immunoexpression with clinicopathological features, including prognosis, merits further study.

Concentration of hyaluronic acid in primary open-angle glaucoma aqueous humor.

We compared the concentration of hyaluronic acid in the aqueous humor of primary open-angle glaucoma (POAG) patients and non-glaucomatous patients. Aqueous humor samples were obtained from 22 patients just before trabeculectomy for clinically uncontrolled POAG (POAG group). Aqueous humor (0.1 mL) was aspirated by inserting a 26-gauge needle into the anterior chamber. The same procedure was performed for 22 non-glaucomatous patients just before cataract surgery (control group). Immediately after collection, the aqueous humor was stored at -20 degrees C. The concentration of hyaluronic acid was determined by a sensitive, noncompetitive and nonisotopic fluoroassay. The median (range) concentrations of hyaluronic acid of the POAG and control groups were 298.4 microg L(-1) (99.0-743.7 microg L(-1)) and 545.1 microg L(-1) (145.0-2366.0 microg L(-1)), respectively. The difference in concentrations of hyaluronic acid between the groups was statistically significant (P<0.001). In conclusion, the concentration of hyaluronic acid in the aqueous humor in POAG patients is lower than in non-glaucomatous patients. Further studies are necessary to determine the role of hyaluronic acid in the pathophysiology of POAG.

Secretion of hepatocyte growth factor and vascular endothelial growth factor during uveal melanoma-monocyte in vitro interactions.

Host-tumour interactions in uveal melanoma, and their involvement in the biological events leading to metastasis and eventually mortality, are not well understood. It is known that uveal melanoma disseminates predominantly via a haematogenous route with metastasis developing primarily in the liver. Therefore, cytokines involved in angiogenesis, such as vascular endothelial growth factor (VEGF), and those expressed in large quantities within the liver, such as hepatocyte growth factor (HGF), are of particular interest in uveal melanoma research. This study investigated the levels of HGF and VEGF in monocyte and uveal melanoma-conditioned medium. Five human uveal melanoma cell lines and one monocyte cell line were seeded in six-well plates. After 18 h, melanoma-conditioned medium (MCM) was placed on the monocyte cell line and monocyte-conditioned medium (MoCM) was placed on each uveal melanoma cell line. Tumour cells and monocytes incubated in fresh, as opposed to conditioned, medium after 18 h were used as controls. VEGF and HGF levels were determined by immunoassay prior to media transfer and 6, 12, 24 and 36 h thereafter. Both cytokines showed an upregulation of expression from all cells after incubation in conditioned medium. 28SC incubated in MCM expressed higher levels of the given cytokines than did uveal melanoma cells incubated in MoCM. In addition, each cell line exhibited a distinct pattern of expression, with individual cell lines exhibiting different peak levels of cytokine production at different time points. These results offer insight into the upregulation of VEGF and HGF, which may play a role in tumour-host cell interactions.