Purpose

Using fluorescence in situ hybridization (FISH) and high-density single nucleotide polymorphism (SNP) mapping genome array, we comparatively evaluated chromosome 3 status and other chromosomal aberrations within a series of choroidal melanomas biopsied by fine needle aspiration (FNAB).

Methods

Transscleral FNAB was performed in 59 patients (59 eyes) who had a clinical diagnosis of choroidal melanoma. Biopsies were processed for chromosome 3 status by centromeric interphase FISH, cytopathology, cell culture, and simultaneous genomic DNA and RNA mapping array analysis.

Results

FISH yielded chromosome 3 status in 38 of 59 (64%) eyes, while high-density SNP mapping array yielded chromosome 3 status in 43 of 59 (73%) eyes. Monosomy 3 was detected by FISH in 15 of 38 (39%) cases, and high-density SNP mapping array data confirmed the finding in 13 of the 15 cases. Furthermore, high-density SNP mapping array revealed five additional cases of significant chromosome 3 aberration not detected by FISH. High-density genomic mapping also provided detailed patterns of chromosomal gain and loss on chromosomes 1, 6, 8, and 9 which segregated into two groups characterized by either monosomy 3 or chromosome 6p gain.

Conclusions

High-density SNP mapping array was better than FISH in detecting chromosome 3 aberrations and monosomy in our melanoma samples. More importantly, the mapping arrays detected additional patterns of chromosomal aberration, which suggest specific pathways for cytogenetic rearrangements in choroidal melanoma and may improve prognostic testing.

The authors present the multimodal imaging findings of an unusual case of bilateral acquired progressive myelination of the optic disc during a 10-year follow-up period in a hyperopic adolescent patient in the absence of an underlying ocular or systemic abnormality. Myelination of the left optic disc was noted at age 7 and of the right optic disc at age 13, but no other ocular or systemic abnormalities were identified. Cross-sectional optical coherence tomography (OCT) and en face OCT angiography confirmed the presence of myelination of the retinal nerve fiber layer and excluded other etiologic possibilities including an astrocytic hamartoma. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e147-e150.].

Retinal cavernous hemangiomas are rare vascular anomalies, and can be associated with cerebral cavernous malformations (CCM). Distinct mutations have been reported in patients who have both CCMs and retinal cavernous hemangiomas. Fluorescein angiography, spectral domain optical coherence tomography, and genetic testing were performed on a patient with a retinal cavernous hemangioma and a CCM. Our patient was heterozygous in the KRIT1/CCM1 gene for a frameshift mutation, c.1088delC. This would be predicted to result in premature protein termination. We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma. We hypothesize that the occurrence of retinal cavernous hemangiomas and CCMs is underlaid by a common mechanism present in the KRIT1/CCM1 gene.

In the United States, more than 25 million adults have diabetes, 40% of diabetics have diabetic retinopathy, and diabetes is the leading cause of blindness in people 20 to 74 years of age. Clinical trials have shown that strict control of blood glucose level and other risk factors delays diabetic retinopathy onset, progression, and vision loss. Patients with Type 1 or Type 2 diabetes mellitus, access to an Apple iPhone or iPad, and no psychological or medical condition that would interfere with the study participated in a nonrandomized clinical trial using SightBook™, a free mobile app that enables self-measurement of visual function and creates a password-protected web account for each patient. Sixty patients enrolled in the clinical trial over a 6 month period. Twenty-six participants were men and 34 were women, with ages from 23 to 72 years (mean 45 ± 15) and diabetes duration of 1.5 to 50 years (mean 15.5 ± 11.5). Thirty-nine (65%) patients reported Type 1 diabetes and 21 (35%) patients reported Type 2 diabetes. Every patient established a personal web account on SightBook and invited participation of treating physicians; 51 (85%) patients completed the validated self-reported outcome assessments. Diabetologist examinations of 49 (82%) patients demonstrated systolic hypertension (≥140 mgHg) in 20% and hemoglobin A1c ≥ 7.0% in 56%. Ophthalmology examinations of 45 patients showed visual acuity in the worse-seeing eye of < 20/40 in 18% and diabetic retinopathy in 42% of patients. This clinical trial used a mobile health app to incorporate diabetic patient self-measurement of vision and coordinate the diabetic patient, diabetologist, and ophthalmologist for control of diabetes and diabetic retinopathy risk factors.

To determine if choroidal melanoma patients want cytogenetic prognostic information. Ninety-nine choroidal melanoma patients completed a questionnaire regarding their opinions about receiving prognostic information. The perceived usefulness of prognostic information was evaluated in patients who had undergone cytogenetic testing. Depressive symptoms, quality of life, and interest in supportive counseling during test receipt were assessed. Ninety-seven percent of respondents reported that they would have wanted prognostic information at the time of their treatment and 98% of respondents reported that supportive counseling should be offered when prognostic information is given. Patients who had received a more favorable prognostic result were more likely to endorse the usefulness of cytogenetic testing than were patients who had received a less favorable prognostic result. Psychological status did not vary significantly as a function of cytogenetic test result. Prognostic information was important to patients with choroidal melanoma, even in the absence of prophylactic measures which might improve prognosis.

Purpose

To report visual acuity, contrast sensitivity and color vision prior to, 1 year after, 2 years after and 3 years after iodine-125 brachytherapy for choroidal and ciliary body melanoma (CCM).

Design

Prospective interventional case series.

Participants

Thirty-seven patients (37 eyes) with CCM.

Methods

Patients had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, Pelli-Robson contrast sensitivity and Hardy-Rand-Rittler color vision measurement; comprehensive ophthalmology examination; optical coherence tomography; and ultrasonography at baseline prior to, 1 year after, 2 years after and 3 years after I-125 brachytherapy.

Main outcome measures

Visual acuity, contrast sensitivity and color vision prior to, 1 year after, 2 years after and 3 years after brachytherapy.

Results

Nineteen (19) men and 18 women with mean age of 58 years (SD 13, range 30-78) prior to, 1 year after, 2 years after and 3 years after brachytherapy had mean best-corrected visual acuity of 77 letters (20/32), 65 letters (20/50), 56 letters (20/80) and 47 letters (20/125); contrast sensitivity of 30, 26, 22 and 19 letters; color vision of 26, 20, 17 and 14 test figures, respectively. Decrease in visual acuity, contrast sensitivity and color vision was statistically significant from baseline at 1 year, 2 years, and 3 years after brachytherapy. Decreased acuity at 3 years was associated with mid-choroid and macula melanoma location, ≥ 4.1 mm melanoma height, radiation maculopathy and radiation optic neuropathy.

Conclusion

1, 2 and 3 years after brachytherapy, eyes with CCM had significantly decreased visual acuity, contrast sensitivity and color vision.

Background

CTLA4-blocking antibodies induce tumor regression in a subset of patients with melanoma. Analysis of immune parameters in peripheral blood may help define how responses are mediated.

Methods

Peripheral blood from HLA-A*0201-positive patients with advanced melanoma receiving tremelimumab (formerly CP-675,206) at 10 mg/kg monthly was repeatedly sampled during the first 4 cycles. Samples were analyzed by 1) tetramer and ELISPOT assays for reactivity to CMV, EBV, MART1, gp100, and tyrosinase; 2) activation HLA-DR and memory CD45RO markers on CD4+/CD8+ cells; and 3) real-time quantitative PCR of mRNA for FoxP3 transcription factor, preferentially expressed by T regulatory cells. The primary endpoint was difference in MART1-specific T cells by tetramer assay. Immunological data were explored for significant trends using clustering analysis.

Results

Three of 12 patients eligible for immune monitoring had tumor regression lasting > 2 years without relapse. There was no significant change in percent of MART1-specific T cells by tetramer assay. Additionally, there was no generalized trend toward postdosing changes in other antigen-specific CD8+ cell populations, FoxP3 transcripts, or overall changes in surface expression of T-cell activation or memory markers. Unsupervised hierarchical clustering based on immune monitoring data segregated patients randomly. However, clustering according to T-cell activation or memory markers separated patients with clinical response and most patients with inflammatory toxicity into a common subgroup.

Conclusion

Administration of CTLA4-blocking antibody tremelimumab to patients with advanced melanoma results in a subset of patients with long-lived tumor responses. T-cell activation and memory markers served as the only readout of the pharmacodynamic effects of this antibody in peripheral blood.

Clinical trial registration number

NCT00086489.