Differences in glucose metabolic activity in liver metastasis separates two groups of metastatic uveal melanoma patients with different prognosis.

BACKGROUND: Uveal melanoma metastasizes to the liver. We aimed to explore the metabolic activity of liver metastases (LM) as a biomarker for survival. METHODS: We analyzed newly diagnosed patients with metastatic UM (MUM) with LM detected by liver-directed imaging and had undergone a PET/CT at diagnosis. FINDINGS: 51 patients were identified between 2004 and 2019. Median age was 62 years, 41% male and 22% ECOG ≥1. LDH, ALP, and GGT were elevated in 49%, 37%, and 57% of patients. Median LM SUVmax was 8.5 (3-42.2). Same size lesions presented a wide range of metabolic activity. Median OS was 17.3 m (95% CI:10.6-23.9). Patients with SUVmax ≥8.5 had an OS of 9.4 m (95% CI:6.4-12.3), whereas patients with SUVmax <8.5 had an OS of 38.4 m (95% CI:21.4-55.5; p < 0.0001, HR = 2.9). We observed similar results when studying M1a disease separately. Multivariate analysis showed SUVmax as an independent prognostic factor for the whole population and those with M1a disease. INTERPRETATION: Increased metabolic activity of LM seems to be an independent predictor of survival. MUM is a heterogeneous disease and metabolic activity probably reflects a different intrinsic behavior.

Survival in small choroidal melanocytic lesions with risk factors managed by initial observation until detection of tumour growth.

BACKGROUND: The main objective was to describe metastatic and survival rates in patients with small choroidal melanocytic lesions initially managed by observation. METHODS: Retrospective, observational study of consecutive cases recruited from 2001 through 2018, followed for a median (mean, range) of 81.0 (89.3, 10-204) months in a tertiary referral centre for ocular oncology. Seventy-five consecutive patients diagnosed with small choroidal melanocytic lesions with risk factors for growth initially observed and who showed progression during follow-up. Treatment was performed (plaque radiotherapy or enucleation in 96% and 4% of cases, respectively) at detection of tumour growth. RESULTS: Median (mean, range) tumour thickness was 2.2 (2.23, 1.08-3.40) mm, and median maximum basal diameter was 8.5 (8.16, 4-12) mm. At diagnosis, a median (mean, range) of 5 (5.48, 1-8) risk factors for progression were present. Lesions grew at a median (mean, range) rate of 0.42 mm/y (1.12, 0-7.68) in thickness and 1.05 mm/y (3.14, 0-4.8) in maximum diameter. Median (mean, range) time until growth was 17.00 (32.6, 1-161) months post-diagnosis, at which time tumours were treated. Five patients developed local recurrence after brachytherapy requiring enucleation. Four patients developed hepatic metastasis. Melanoma-specific survival was 98% at 5 years (95% CI, 94.2-100%) and 91.6% (95% CI, 82-100%) at 10 and 15 years. CONCLUSION: In small melanocytic lesions with risk factors for growth, initial observation until detection of tumour growth results in a seemingly low risk of metastasis, suggesting that this may be an initial approach to consider in tumours with indeterminate malignant potential.

INTERNAL LIMITING MEMBRANE PEELING VERSUS NONPEELING TO PREVENT EPIRETINAL MEMBRANE DEVELOPMENT IN PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: A Swept-Source Optical Coherence Tomography Study With a New Postoperative Classification System.

PURPOSE: To determine whether internal limiting membrane peeling in primary rhegmatogenous retinal detachment prevents epiretinal membrane (ERM) development. Secondarily, we propose a classification system for postoperative ERMs. METHODS: Retrospective, interventional, comparative case series. Consecutive eyes with primary rhegmatogenous retinal detachment (n = 140) treated by a single surgeon. The presence of postoperative ERMs was assessed with swept-source optical coherence tomography. RESULTS: An ERM was detected in 26 eyes (46.4%) in the nonpeeling group and in one eye (1.8%) in the internal limiting membrane peeling group (P ≤ 0.001). The median visual acuity significantly improved in both groups (P ≤ 0.001). Inner retinal dimples were observed in 41.1% of eyes in the internal limiting membrane peeling group versus 0% in the nonpeeling group (P ≤ 0.001), and they were not correlated with visual acuity (r = 0.011; P = 0.941). Based on swept-source optical coherence tomography findings, we identified three different types of ERMs: 7 (26.9%) were classified as Type 1, 12 (46.1%) as Type 2, and 7 (26.9%) as Type 3. Superficial retinal plexus deformations observed on optical coherence tomography angiography and en face images were detected in 100% of Type 3 ERMs, 41.6% of Type 2, and 0% of Type 1 (χ = 14.3; P = 0.001). Interestingly, all of the patients who presented these alterations also had metamorphopsia. CONCLUSION: Internal limiting membrane peeling in primary rhegmatogenous retinal detachment seems to prevent postoperative ERM development. Swept-source optical coherence tomography analysis is helpful to define and classify different types of ERMs and to establish the surgical indication for their removal.

DNA Methylomes Reveal Biological Networks Involved in Human Eye Development, Functions and Associated Disorders.

This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors. Main conclusions allow certifying that crucial pathways related to Wnt-MAPK signaling pathways or neuroinflammation are epigenetically controlled in the fibrotic disorders involved in retinal detachment, but results also reinforced the contribution of neurovascularization (ETS1, HES5, PRDM16) in diabetic retinopathy. Finally, we had studied the methylome in the most frequent intraocular tumors in adults and children (uveal melanoma and retinoblastoma, respectively). We observed that hypermethylation of tumor suppressor genes is a frequent event in ocular tumors, but also unmethylation is associated with tumorogenesis. Interestingly, unmethylation of the proto-oncogen RAB31 was a predictor of metastasis risk in uveal melanoma. Loss of methylation of the oncogenic mir-17-92 cluster was detected in primary tissues but also in blood from patients.

Structure versus function: correlation between outer retinal and choroidal thicknesses measured by swept-source OCT with multifocal electroretinography and visual acuity.

BACKGROUND: To correlate retina-choroidal anatomy as assessed via swept-source OCT (SS-OCT) with retinal function as determined by best-corrected visual acuity (BCVA) and multifocal electroretinogram (mfERG). METHODS: Thirty-three eyes from 33 patients including 16 with neovascular AMD (nvAMD) and 17 controls were included. Patients were included in the present study after a complete ophthalmologic examination, including BCVA, slit-lamp study, intraocular pressure measurement, dilated fundus examination after tropicamide instillation, SD-OCT, SS-OCT, fundus photographs and mfERG. Age, sex, BCVA, number of anti-VEGF intravitreal injections in the nvAMD group, were recollected. Outer retinal and choroidal thickness were determined at the fovea and 500 µm temporal, superior, nasal and inferior. First-order response from mfERG was collected. P1 amplitude was recorded in R1, R2 and the average of R1 + R2. The measurements recollected from the SS-OCT, mfERG and BCVA were compared. RESULTS: Better BCVA was found with thicker outer retina foveal thickness (r = 0.349; P = 0.047), with thicker subfoveal choroidal thickness (r = 0.443; P = 0.010), and with higher amplitude in P1 at R1 (r = 0.346; P = 0.037). Outer retina foveal thickness did not correlate with P1 amplitude at R1 (r = 0.072; P = 0.692), R2 (r = 0.265; P = 0.137) either with the average P1 amplitude at R1 + R2 (r = 0.253; P = 0.156). A thicker subfoveal choroidal thickness was related with higher amplitude in P1 at R1 (r = 0.383; P = 0.028), R2 (r = 0.409; P = 0.018) and the average of R1 + R2 (r = 0.419; P = 0.015). CONCLUSIONS: Choroidal thickness demonstrated a positive correlation with retinal function in the sample studied, so a thicker choroid is related to a better retinal function measured with mfERG and BCVA.

DOME-SHAPED MACULA IN MYOPIC EYES: Twelve-Month Follow-up.

PURPOSE: To study the long-term clinical course of dome-shaped macula in myopic eyes and to evaluate treatment efficacy for subretinal fluid (SRF) as a related complication. METHODS: A retrospective, single-center consecutive case series study was conducted. The authors analyzed myopic eyes with dome-shaped macula in patients who presented for evaluation of decreased vision. Dome-shaped macula was defined as a convexity of the retina-choroidal macular complex seen on spectral domain optical coherence tomography images. All patients were followed for at least 12 months (mean, 25 months). Fluorescein angiography and/or indocyanine green angiography were performed in cases with SRF to rule out choroidal neovascularization. RESULTS: A total of 56 dome-shaped macula eyes from 36 patients were included in the study (bilateral in 55% of patients). Mean patient age was 56.9 ± 13.1 years. The mean spherical equivalent was -9.1 ± 6.0 diopters; 53% of eyes were considered highly myopic (>-6 diopters) and 47% of eyes were mildly myopic. In most cases (37 eyes; 66.1%), the dome-shaped macula was detected on vertical spectral domain optical coherence tomography scan patterns. No significant changes (P ≥ 0.1) were observed in mean best-corrected visual acuity or mean central foveal thickness from baseline to final follow-up. Subretinal fluid was present in 29 eyes (51.8%) at baseline, with no differences in best-corrected visual acuity in eyes with and without SRF (P ≥ 0.05). Nineteen of the 29 SRF eyes were treated: 8 underwent low-fluence photodynamic therapy, whereas 7 received bevacizumab, and 4 ranibizumab. No significant differences were found between treated and untreated SRF eyes in best-corrected visual acuity improvement (P ≥ 0.1), or complete resolution of SRF (P ≥ 0.1). Likewise, photodynamic therapy did not yield any significant benefit versus untreated eyes in best-corrected visual acuity or improvement of SRF. CONCLUSION: Dome-shaped macula is a condition associated with myopic eyes that seems to remain stable over time in terms of vision and macular profiles. It is often associated with chronic SRF, for which no effective treatment is current available. However, SRF does not seem to be a significant cause of visual impairment.

Tumor Volumes in Choroidal Melanoma: Agreement Between Three-Dimensional Ultrasound and Two Mathematical Models.

PURPOSE: To determine the degree of agreement between 2 mathematical models and 3-dimensional ultrasonography (3DUS) in estimating choroidal melanoma tumor volumes. DESIGN: Reliability analysis. METHODS: Tumor measurements estimated by 2 mathematical models (designated Formula 1 and Formula 2) were compared to those obtained by 3DUS in 45 consecutive patients with primary choroidal melanoma to determine the percentage agreement between the models and 3DUS. RESULTS: Both formulas tended to overestimate the tumor volume. Overall, the mean volume differences between 3DUS and Formula 1 and between 3DUS and Formula 2, respectively, were 51.7 mm(3) (95% confidence interval [CI], 187.6 to 84.3) and 23.8 mm(3) (95% CI, 122.5 to 74.8). Excluding mushroom-shaped tumors, the mean volume differences were 52.0 mm(3) (95% CI, 194.9 to 91.0) and 23.0 mm(3) (95% CI, 127.0 to 81.0), respectively. In mushroom-shaped tumors, mean volume differences were 49.9 mm(3) (95% CI, 135.7 to 35.9) and 29.3 mm(3) (95% CI, 87.6 to 29.0), respectively. CONCLUSIONS: The agreement between these mathematical models and the measured 3DUS volume was high. The data obtained in this study show that both formulas provide a simple, fast, and accurate method of estimating tumor volumes in the clinical setting, suggesting that these models could be used as a reliable and inexpensive alternative to time-consuming procedures such as 3DUS or magnetic resonance imaging. The accurate tumor volume values provided by these formulas may help to provide more reliable estimates of tumor regression or regrowth following globe-preserving treatment of choroidal melanomas, and may be a valuable prognostic indicator.

The Prevalence of Vitreomacular Interface Pathology in a Spanish Tertiary Hospital.

PURPOSE: To determine the prevalence of vitreomacular interface (VMI) pathology, using spectral-domain optical coherence tomography (SD-OCT). METHODS: VMI status was classified into macular posterior vitreous detachment (PVD), focal vitreomacular adhesion (VMA; ≤1,500 µm), broad VMA (>1,500 µm), focal vitreomacular traction (VMT; ≤1,500 µm), broad VMT (>1,500 µm), full-thickness macular hole (FTMH) with the presence of VMT, and FTMH without the presence of VMT. RESULTS: A total of 1,976 eyes were included. A nonpathologic VMI was observed in 1,875 eyes (94.8%), including 1,050 (53.1%) with PVD, 120 (6.1%) with focal VMA and 705 (35.6%) with broad VMA. A pathologic state of the VMI was diagnosed in 101 eyes (5.1%). Thirty-three eyes (1.7%) were classified as focal VMT, 29 (1.4%) as broad VMT, 39 (1.9%) as FTMH, resulting in 6 small, 12 medium and 21 large FTMHs, six eyes had VMT associated to FTMH. CONCLUSIONS: Even in a tertiary care, retinal referral practice, VMI pathology is a relatively rare condition. There was a higher prevalence in a tertiary hospital study compared to population-based studies.

En face mode of swept-source optical coherence tomography in circumscribed choroidal haemangioma.

PURPOSE: To describe the findings in circumscribed choroidal haemangioma (CCH) using en face swept-source optical coherence tomography (SS-OCT). METHODS: En face images were obtained employing DRI-1 Atlantis OCT (Topcon, Tokyo, Japan), using a three-dimensional volumetric scan of 12×9 mm. Images were obtained from the retinal pigment epithelium to 1000 µm in depth of the tumour. RESULTS: Twenty-two eyes from 22 patients with the clinical diagnosis of CCH were included. In 20 eyes (90.9%), a characteristic pattern was visualised in the en face image across the vascular tumour. A multilobular pattern, similar to a honeycomb, with hyporeflective, confluent, oval or round areas corresponding with the lumen of the tumour vascular spaces, and hyper-reflective zones, which may represent the vessels walls and connective tissue of the tumour. Ten eyes (45.4%) showed a hyper-reflective halo surrounding the tumour. Seventeen tumours (77.2%) showed small diameter vessels at the inner zone and larger vessels in the outer area. Twelve patients (54.5%) had previously received treatment (photodynamic therapy, transpupillary thermotherapy, dexamethasone intravitreal implant or brachytherapy with ruthenium-106). No differences were found between treated and untreated patients in any of the measured parameters. CONCLUSIONS: En face SS-OCT is a rapid, non-invasive, high-resolution, technology, which allows a complementary study to cross-sectional scans in CCH. A characteristic multilobular pattern, with a hyper-reflective halo surrounding the tumour, was found in en face SS-OCT images. No morphological differences were found between naïve patients and patients who received previous treatment.

Swept source optical coherence tomography imaging of a series of choroidal tumours.

OBJECTIVE: This pilot study aimed to describe the swept-source optical coherence tomography (SS-OCT) features of a series of choroidal tumours. DESIGN: This was an observational case series. PARTICIPANTS: Patients in our ocular oncology unit were recruited: 32 eyes belonging to 31 patients. METHODS: All of the patients underwent fundus photography, ultrasonography (US), fundus autofluorescence (FAF), and SS-OCT. The main assessed characteristics were maximal tumour diameter and thickness, inner structure, and disturbances in the choroidal layers, sclera, retinal pigment epithelium, and retina. RESULTS: The tumours examined consisted of 16 nevi, 6 lesions with risk factors for growth, 4 melanomas, 4 hemangiomas, and 2 choroidal metastases. SS-OCT provided an accurate measurement of the tumour's maximum diameter in every case. Choroidal nevi displayed a compact, regular structure with a preserved choriocapillaris. Choroidal melanomas showed a more irregular inner structure, with an ablated choriocapillaris. Choroidal hemangiomas had a regular spongelike pattern. Choroidal metastases had an irregular inner structure organized in clumps and an ablated outer retina. In most of the pigmented tumours, the sclerochoroidal interface was not identifiable by SS-OCT. The presence of lipofuscin, detected by funduscopy and FAF, was also correlated with the SS-OCT findings. CONCLUSIONS: SS-OCT provided a view of the inner structures of a series of choroidal tumours and assessed their associated structural anomalies, as well as obtained measurements of the diameter and thickness in most cases.

En face swept-source optical coherence tomography in neovascular age-related macular degeneration.

PURPOSE: To describe en face swept-source optical coherence tomography (SS-OCT) findings in the retinal pigment epithelium (RPE) and choroid and to correlate them with fluorescein angiography (FA) and/or indocyanine green angiography (ICGA) in neovascular age-related macular degeneration (AMD). METHODS: Thirty-eight eyes with the recent diagnosis of neovascular AMD were imaged using an SS-OCT system. En face images were obtained at RPE, choriocapillaris, Sattler's layer and Haller's layer level. Analysis of the images and correlation with colour fundus photographs, FA, ICGA in selected cases, were made. RESULTS: En face images at RPE level revealed changes in all eyes. The neovascular complex appeared hyper-reflective in 9 of 38 eyes (23.7%), and in 29 of 38 eyes (76.3%), it was hyporeflective. The choriocapillaris en face image showed pathological changes in all eyes as well, and in 20 out of 38 eyes (52.6%), the alterations were hyper-reflective, while 18 of 38 eyes (47.4%) showed hyporeflective changes. Twenty (52.6%) eyes and 19 (50.0%) had a hyper-reflective lesion in Sattler's layer and Haller's layer, respectively, and 15 (39.4%) cases showed a hyporeflective lesion in both layers. No differences were found between the neovascular complex area, horizontal and vertical diameters, measured in the en face image and FA (p=0.171, p=0.061, p=0.133, respectively). Hyporeflective changes were predominant at RPE level and hyper-reflective at choriocapillaris, Sattler's and Haller's layers. CONCLUSIONS: En face SS-OCT is a rapid, non-invasive, high-resolution, promising technology, which allows a complementary study to angiography of neovascular AMD. There is a correlation between angiography and en face SS-OCT images in neovascular AMD.

Endoresection versus iodine-125 plaque brachytherapy for the treatment of choroidal melanoma.

PURPOSE: To compare the effectiveness of pars plana vitrectomy endoresection with iodine-125 brachytherapy in the treatment of choroidal melanoma. DESIGN: A nested case-control study (1:2) from a surgical cohort. METHODS: The study comprised 81 choroidal melanoma patients treated with either endoresection or iodine-125 brachytherapy. Twenty-seven patients who had undergone endoresection were matched according to tumor height and postequatorial tumor location with 54 cases treated with iodine-125 brachytherapy. Metastatic disease, overall survival, local tumor recurrence, visual acuity, and secondary enucleation rates were analyzed and compared between groups. RESULTS: Metastatic spread was observed in 11 patients in the iodine-125 brachytherapy group vs only 1 patient in the endoresection group (20.4% and 3.7%, respectively, P = .053). Fourteen patients died during follow-up: 11 in the brachytherapy arm vs 3 in the endoresection arm (20.4% and 11.1%, respectively, P = .238). For the iodine-125 brachytherapy and endoresection groups, respectively, the 5-year Kaplan-Meier estimates were as follows: overall survival, 81.5% vs 89.2% (log-rank test, P = .429;); relapse-free survival, 96.6% vs 92.4% (P = .2); visual acuity retention equal or superior to 20/200, 66.4% vs 59.9% (P = .083), and eye retention, 85.7% vs 87.8% (P = .942). CONCLUSIONS: Endoresection for choroidal melanoma is an effective treatment modality in selected cases of posterior choroidal melanomas, with outcomes similar to those obtained with iodine-125 brachytherapy.

One-year results of a flexible regimen with ranibizumab therapy in macular degeneration: relationship with the number of injections.

PURPOSE: To evaluate the efficacy and safety of a flexible regimen with intravitreal injections of ranibizumab in patients with naive choroidal neovascularization secondary to age-related macular degeneration and to determine whether the final outcome is related to the number of injections. METHODS: Prospective, noncomparative, consecutive case series study. We included 90 eyes of 88 patients that were initially treated with 3 consecutive monthly intravitreal injections of ranibizumab, and thereafter, follow-up visits were progressively spread out to a maximum of 8 weeks apart in the absence of visual acuity loss and signs of lesion activity. The primary end points were changes in visual acuity (Early Treatment Diabetic Retinopathy Study letters), foveal thickness measured by spectral-domain optical coherence tomography, and lesion size (LS) measured by fluorescein angiography. RESULTS: The median visual acuity improved from 53 letters at baseline to 60 letters at Month 1 (P < 0.0001), 63 letters at Month 3 (P < 0.0001), and 60 letters at Month 12 (P < 0.0001). A significant reduction was also observed in foveal thickness and LS (P < 0.0001). The mean number of injections was 4.4, and the mean number of visits was 8.0. Treatment consisted of 3 injections for 40% of patients, and 60% of patients received more than 3 injections. No significant association was observed between the visual acuity improvement and the number of injections. No relevant side effects were observed. CONCLUSION: A flexible regimen with ranibizumab therapy is efficacious and safe in patients with neovascular age-related macular degeneration, reducing both the burden of injections and follow-up visits. The visual acuity improvement was independent of the number of injections.