Characterizations of uveal melanoma patients with three additional primary malignancies.

PURPOSE: In a population-based cohort of 960 uveal melanoma (UM) patients, we describe patients with three additional malignancies, including one unique patient with four synchronous primary malignancies. METHOD: A descriptive presentation of the clinical course and outcome for UM patients with three additional primary malignancies. RESULTS: After more than 20 years of follow-up of the UM cohort, 11 patients (1.1%) were diagnosed with three additional primary malignancies before, simultaneously or after UM. Among these, one patient had four synchronous primary malignancies, detected during workup for a symptomatic UM. All diagnoses were treated during the following 4 months, firstly the breast cancer, thereafter, the lung and pancreatic cancers and finally the UM. The patient died 3 years later of abdominal carcinomatosis due to the pancreatic cancer. The family history and gene testing did not disclose any genetic predisposition for cancer. A comparison of the four synchronous tumours, morphologically and immunohistochemically, showed no similarities and the expression of antibodies was different. CONCLUSION: Patients with UM may be diagnosed with non-ocular additional primary cancers. Thus, a comprehensive workup is obligatory and a further follow-up of the UM patients seems necessary. The UM is not always the main problem.

Macular hole Delphi consensus statement (MHOST).

PURPOSE: To derive a Delphi method-based consensus for the surgical management of Full Thickness Macular Hole (FTMH) and Lamellar Macular Hole (LMH). METHODS: 37 expert VR surgeons from 21 mainly European countries participated in Delphi method-based questionnaire for diagnosis and treatment of FTMHs and LMHs. RESULTS: A total of 36 items were rated in round 1 by 37 participants, of which 10 items achieved consensus: intraoperative verification of PVD; clinical superiority of OCT-based FTMH classification; practical ineffectiveness of ocriplasmin; circular 360° ILM peeling for small macular holes; use of regular surgical technique for the size of the hole in concomitant retinal detachment; performing complete vitrectomy; SF6 gas as preferred tamponade; cataract surgery if crystalline lens is mildly/moderately opaque; removal of both ILM and LHEP in LMH surgery. In round 2, 18 items with moderate consensus (45-70% agreement) in round 1 were rated by 35 participants. Final consensus was reached in 35% of questions related to both diagnosis and surgical procedures. CONCLUSIONS: This Delphi study provides valuable information about the consensus/disagreement on different scenarios encountered during FTMH and LMH management as a guide tosurgical decision-making. High rate of disagreement and/or variable approaches still exist for treating such relatively common conditions.

Primary vitrectomy or intravitreal antibiotics followed by early vitrectomy for acute endophthalmitis: A prospective observational study.

BACKGROUND/AIMS: To compare outcomes of acute endophthalmitis (EO) managed with either primary vitrectomy (PV) or primary intravitreal antibiotics (vancomycin and ceftazidime) followed by early vitrectomy (PIAEV) combined with polymerase chain reaction (PCR)-based diagnostics. METHODS: This was a prospective, comparative observational study of acute EO cases admitted to a regional vitreoretinal service over 18 months. Depending on whether immediate vitrectomy (within 6 h) was achievable, the EO cases were treated with either (1) PV or (2) PIAEV. Microbiology samples were collected either (A) before or (B) after administration of intravitreal antibiotics. The samples were analysed with broad-range 16S PCR and culture. RESULTS: The study included 41 EO cases. There were 19 post-injection EO, 18 post-cataract EO, three post-vitrectomy EO, and one blebitis-related EO. Fifteen of 19 PV cases and 15 of 21 PIAEV had a clinically meaningful improvement in best-corrected visual acuity (BCVA) of at least 15 letters at 3 months (p = 0.58). One patient was lost to follow-up. Twenty-three cases were culture- and PCR-positive, and seven additional cases were culture-negative but PCR-positive (p = 0.02). PCR increased the diagnostic yield for samples collected both before and after administration of intravitreal antibiotics. CONCLUSION: Primary vitrectomy or PIAEV allowed for vitrectomy for all cases of acute EO in a large region. Most eyes in both groups achieved a clinically meaningful improvement in BCVA. By combining culture with PCR in connection with the vitrectomy procedure, intravitreal antibiotics could be injected before microbiological sampling, thereby improving the door-to-treatment time without sacrificing microbial identification.

Fundus Autofluorescence Change as an Early Indicator of Treatment Effect of Brachytherapy for Choroidal Melanomas.

BACKGROUND: Early confirmation of the effect of brachytherapy for choroidal melanoma showing that tumour coverage is valuable. The irradiated retinal pigment epithelium (RPE) commonly develops atrophy. This study compares the fundus autofluorescence (AF) changes to the development of RPE atrophy following brachytherapy. METHODS: Retrospective study of 19 patients treated with 106Ru and 2 with 125I plaques with either a 3- or 6-month follow-up period. Ultra-widefield (UW) composite colour and AF images were obtained with Optomap 200Tx and interpreted as complete, partial, or no RPE changes and complete or partial hyperautofluorescence, hypoautofluorescence, or isoautofluorescence. RESULTS: At the 3-month follow-up, 9 of 13 patients (69%) (95% confidence interval [CI], 0.389-0.896) treated with 106Ru plaques developed complete homogenous hyperautofluorescence surrounding the tumour, but only 1 of 13 (8%) (95% CI, 0.004-0.379) developed complete RPE atrophy at the same time point. Six patients in the 106Ru plaque group had their first follow-up with UW imaging at 6 months. Four of them developed homogenous hyperautofluorescence and none developed complete RPE atrophy around the tumour. The 2 patients treated with 125I did not demonstrate any clear RPE or AF changes. CONCLUSION: The effect of 106Ru plaque treatment on fundus UW imaging is detected as homogenous and well-demarcated hyperautofluorescence before visible RPE atrophy.

The Results of Stricter Inclusion Criteria in an Immunomagnetic Detection Study of Micrometastatic Cells in Bone Marrow of Uveal Melanoma Patients - Relevance for Dormancy.

Approximately 50% of uveal melanoma patients develop metastases. We want to evaluate the effect of stricter criteria on our data from our previous study correlating survival and bone marrow (BM) micrometastasis results using our immunomagnetic separation (IMS) method. Mononuclear cell fractions (MNC) isolated from BM were examined for tumour cells and the patients were classified as BM positive (BM+) or BM negative (BM-). The study originally included 328 consecutive patients with uveal melanoma from 1997 to 2006. The cohort was limited to 217 patients when we introduced cyto- or histopathological verification of melanoma cells in the patient as a main new criterion for inclusion. Tumour cells were found in BM-samples in 38.7% (95% CI, 32-45) at enrolment. Until the latest work-up 43.8% (95% CI, 38-50) of patients had developed melanoma metastases. After a minimum follow-up time of 8.5 years, 60.4% (95% CI, 54-66) of patients had died. The causes were: melanoma metastases 69.5%, another type of cancer 5.4% and non-cancerous causes 19.5%. Overall median survival was shorter for the BM- patients (11.3 years) (95% CI, 10-12) compared to the BM+ (16.5 years) (95% CI, 12-14), p = 0.04, log rank test. All-cause mortality and specific melanoma mortality estimated after 12 year follow-up showed a highly significant difference comparing BM- and BM+, p = 0.010 and p = 0,017, respectively. IMS yields a high fraction of BM+ samples due to micrometastasis at diagnosis and these cells appear to have a positive prognostic impact strengthening our previous report. The late recurrences support the concept of tumour dormancy.

Two-year functional and anatomical results after converting treatment resistant eyes with exudative age-related macular degeneration to aflibercept in accordance with a treat and extend protocol.

PURPOSE: To study the effects of converting to aflibercept in accordance with a treat and extend (T&E) strategy in eyes with treatment resistant exudative age-related macular degeneration (AMD). METHODS: Two-year prospective study of eyes with exudative AMD and persistent macular fluid despite monthly treatment with ranibizumab or bevacizumab. Eyes were converted to 2.0 mg aflibercept in accordance with a T&E protocol. RESULTS: Fifty eyes from 47 patients were included. At baseline, the mean central retinal thickness (CRT) was 273 µm and mean best-corrected visual acuity (BCVA) 0.25 logarithm of the minimal angle of resolution (logMAR). The mean number of aflibercept injections the first year was 9.2. After 1 year, there was a reduction in mean CRT to 228 µm (p < 0.001); 22 eyes (44%) had a dry macula; and the mean BCVA was 0.24 logMAR (p = 0.531). The mean number of aflibercept injections the second year was 8.0 (p = 0.013 compared to first year). After 2 years, 24 eyes (48%) received treatment more frequently than every eighth week. The mean CRT was 225 µm (p < 0.001 compared to baseline); 31 eyes (62%) had a dry macula; and mean BCVA was 0.32 logMAR (p = 0.005 compared to baseline). Five eyes did not complete 2 years of aflibercept treatment after failing to improve. CONCLUSION: A majority of eyes showed improved anatomic outcomes. There was a small decrease in mean BCVA after the second year of treatment. About half of the eyes required treatment more frequently than the recommended aflibercept label of an 8-week interval.

Immunomagnetic detection of micrometastatic cells in bone marrow of uveal melanoma patients: a paradox.

PURPOSE: Our objective was to study survival rates with the bone marrow (BM) results in a cohort of uveal melanoma patients with long follow-up. METHODS: Mononuclear cell fractions isolated from BM were examined for tumour cells using our immunomagnetic separation (IMS) method. The patients were classified as BM positive or BM negative. Clinical follow-up, histopathological findings, vital status and cause of death were registered. RESULTS: The study included 328 consecutive patients with uveal melanoma from 1997 to 2006. Tumour cells were found in BM samples in 29% (95% CI, 25-34) at enrolment (96 cases). After a minimum follow-up time of 6 years, 156 (48%) (95% CI, 42-53) melanoma patients had died. The causes were as follows: melanoma metastases 92 (59%), another cancer 20 (13%) and non-cancer 44 (28%). Nine patients were still living with melanoma metastases. Until the latest work-up, 101(31%) (95% CI, 26-36) patients had developed melanoma metastases. Cyto- or histopathological verification of the metastatic lesions was obtained in 85 cases (84%). In the group with melanoma metastases, 28 tested BM positive at study entry (28%) (95% CI, 19-38). In total, 39 of 101 with metastases tested positive at least once after a maximum of three tests (39%) (95% CI, 29-49). The overall median survival from the first BM test was shorter for the BM negative patients (9.5 years) compared with the BM positive (14.4 years), p = 0.02, log rank test. CONCLUSION: Ocular melanoma cells detected in BM seem to have a positive prognostic impact on survival in contrast to our original hypothesis.

Disseminated tumour cells in bone marrow of patients with uveal melanoma.

PURPOSE: Approximately 50% of patients with uveal melanomas develop metastases. Thus, it is important to improve our understanding of how melanoma metastases develop. METHODS: As part of a uveal melanoma micrometastasis study, we compared the detection rates of immunomagnetically selected (IMS) tumour cells in bone marrow (BM) with positively stained tumour cells using immunocytochemistry (ICC). Bone marrow mononuclear cells were isolated. Immunocytochemistry cytospin preparations were immunocytochemically stained in parallel with two different melanoma antibodies, 9.2.27 and HMB45. Using IMS, melanoma cells were selected from BM mononuclear cell fractions using immunomagnetic beads coated with the 9.2.27 antibody and identified by light microscopy. RESULTS: In cytospin preparations from 226 patients, melanoma cells were detected in 24 (10.6%), 10 with 9.2.27 and 17 with the HMB45 antibody. In three cases, we found positive cells with both antibodies. Six of the 226 (2.6%) patients that stained positively with ICC died with metastatic disease, all also positive with IMS. Sixty-six (29.2%) patients had positive BM samples with IMS at the first examination. Immunomagnetic selection (IMS) was positive in 36.8% of the 57 patients who later developed clinical metastases. Twenty-one IMS-positive patients and 31 IMS-negative patients died of metastases, in total 52 of 226 patients (23.0%). The mortality rate of melanoma metastasis was 24% (6/24) after at least 4 ½ years in ICC-positive patients compared to 38.5% (20/52) in IMS-positive patients. CONCLUSION: The presence of melanoma cells in BM of patients with uveal melanoma is documented in our study with IMS and ICC. Immunomagnetically selected is more sensitive than ICC in detecting tumour cells in BM. However, statistically, we did not find any prognostic impact of the presence of melanoma cells in BM.