Uveal Melanoma, Angiogenesis and Immunotherapy, Is There Any Hope?

Uveal melanoma is considered a rare disease but it is the most common intraocular malignancy in adults. Local treatments are effective, but the systemic recurrence rate is unacceptably high. Moreover, once metastasis have developed the prognosis is poor, with a 5-year survival rate of less than 5%, and systemic therapies, including immunotherapy, have rendered poor results. The tumour biology is complex, but angiogenesis is a highly important pathway in these tumours. Vasculogenic mimicry, the ability of melanomas to generate vascular channels independently of endothelial cells, could play an important role, but no effective therapy targeting this process has been developed so far. Angiogenesis modulates the tumour microenvironment of melanomas, and a close interplay is established between them. Therefore, combining immune strategies with drugs targeting angiogenesis offers a new therapeutic paradigm. In preclinical studies, these approaches effectively target these tumours, and a phase I clinical study has shown encouraging results in cutaneous melanomas. In this review, we will discuss the importance of angiogenesis in uveal melanoma, with a special focus on vasculogenic mimicry, and describe the interplay between angiogenesis and the tumour microenvironment. In addition, we will suggest future therapeutic approaches based on these observations and mention ways in which to potentially enhance current treatments

Acute onset of retinal detachment after posterior chamber phakic intraocular lens implantation

Case report: a 34-year-old man with severe myopia, presented with acute visual loss in his right eye. This occurred 3 hours after a posterior chamber phakic (PCP) intraocular lens (IOL) implantation, and was associated with a rhegmatogenous retinal detachment. Retinal retachment surgery was performed without complications, with the outcome showing good anatomical and functional results during a 2-year follow-up period. Discussion: despite the fact that several authors have described retinal detachments following PCP IOL implantation in highly myopic patients, there is no evidence that this procedure increases the risk of retinal detachment in these patients. The occurrence of the retinal detachment immediately after the phakic IOL implantation supports the hypothesis that the surgical procedure could induce iatrogenic changes in patients with high myopia, which could increase the incidence of retinal detachment. In contrast to other reports, the interval between the PCP IOL implantation and the retinal detachment was only 3 hours in our patient. We believe this demonstrates the importance of performing a complete preoperative vitreoretinal examination in patients with severe myopia

Two cases of accidental dislocation of the silicone sleeve of an extrusion cannula into the vitreous cavity

Background: fluid-air exchange during vitreoretinal surgery is often used as a tool for subretinal fluid endodrainage. Soft-tipped flexible extrusion cannulas are commonly used to aspirate the posterior subretinal fluid. Methods: this is an observational two-case series describing two patients who underwent 20-G pars plana vitrectomy complicated by the accidental fall of the silicone sleeve of a soft-tipped extrusion cannula into the vitreous cavity. In the first case, the cannula had inadvertently been subjected to sterilization process. Results: while withdrawing the soft-tipped extrusion cannula from the eye, following internal drainage of transvitreal and subretinal fluid, the loose silicone sleeve probably got entangled at the inner lip of the sclerotomy and finally fell on the retinal surface. In both cases, the silicone sleeve was held and removed with an intraocular forceps. Conclusions: this rare complication has been reported in the literature only once previously. Sterilization of disposable subretinal fluid cannulas is not advisable because of the risk of dislocation of the silicone sleeve into the eye. Besides this, it is important to check the integrity of the silicone sleeve before and after surgery

Ocular ultrasonography focused on the posterior eye segment: what radiologists should know

Ocular B-mode ultrasonography (US) is an important adjuvant for the clinical assessment of a variety of ocular diseases. When ophthalmoscopy is not possible, mainly due to opacification of the transparent media (e.g., mature cataract or vitreous haemorrhage), US can guide the ophthalmologist in diagnosing disease and choosing treatment. The superficial location and cystic structure of the eye make US ideal for imaging of the eye. Moreover, dynamic study helps distinguish between various conditions that would otherwise be difficult to differentiate in some clinical setting, such as vitreous, retinal, and choroidal detachment. US is also good technique for detecting other pathologic conditions such as lens dislocation, vitreous haemorrhage, asteroid hyalosis, optic disc drusen, and tumors (e.g., choroidal melanoma, metastases, hemangioma). An understanding of the basic anatomy of the eye, the US technique, and common entities that affect the ocular globe will allow radiologists to offer this valuable imaging modality to patients and referring clinicians. This article focuses on the US anatomy and pathologic conditions that affect the posterior ocular segment

ThicknessTool: automated ImageJ retinal layer thickness and profile in digital images

To develop an automated retina layer thickness measurement tool for the ImageJ platform, to quantitate nuclear layers following the retina contour. We developed the ThicknessTool (TT), an automated thickness measurement plugin for the ImageJ platform. To calibrate TT, we created a calibration dataset of mock binary skeletonized mask images with increasing thickness masks and different rotations. Following, we created a training dataset and performed an agreement analysis of thickness measurements between TT and two masked manual observers. Finally, we tested the performance of TT measurements in a validation dataset of retinal detachment images. In the calibration dataset, there were no differences in layer thickness between measured and known thickness masks, with an overall coefficient of variation of 0.00%. Training dataset measurements of immunofluorescence retina nuclear layers disclosed no significant differences between TT and any observer's average outer nuclear layer (ONL) (p = 0.998), inner nuclear layer (INL) (p = 0.807), and ONL/INL ratio (p = 0.944) measurements. Agreement analysis showed that bias between TT vs. observers' mean was lower than between any observers' mean against each other in the ONL (0.77 ± 0.34 µm vs 3.25 ± 0.33 µm) and INL (1.59 ± 0.28 µm vs 2.82 ± 0.36 µm). Validation dataset showed that TT can detect significant and true ONL thinning (p = 0.006), more sensitive than manual measurement capabilities (p = 0.069). ThicknessTool can measure retina nuclear layers thickness in a fast, accurate, and precise manner with multi-platform capabilities. In addition, the TT can be customized to user preferences and is freely available to download

Intravitreal bevacizumab (Avastin) in the treatment of macular edema secondary to retinal vein occlusion

Objective: to evaluate efficacy and safety of intravitreal injections of bevacizumab in the treatment of macular edema secondary to retinal vein occlusion (RVO). Methods: prospective study, noncomparative, interventional case series. Twelve consecutive patients (12 eyes) with macular edema associated with nonischemic retinal vein occlusion were treated with intravitreal bevacizumab (1.25 mg). All subjects underwent standardized ophthalmic evaluation at baseline and at weeks 1, 4, 12, and 24, consisting of visual acuity (VA) measurement using ETDRS charts, and imaging with ocular coherence tomography evaluating changes in foveal thickness (FT) and macular volume (MV). Results: the median age was 66 years (± 4.16), and the median duration of symptoms was 4 months (± 1.81). There were six cases of inferior branch vein occlusion and six cases of superior branch retinal vein occlusion. Mean VA improved from 1.32 ± 0.24 (logMAR values) at baseline to 0.8 ± 0.15 (p = 0.0003) at the 6-month follow-up. The macular edema responded promptly, and a trend to restoration of normal macular anatomy was observed at by the seventh day. Mean FT improved from 615.50 ± 116.29 microns to 420 ± 72.53 microns (p = 0.001), and the mean MV improved from 19.81 ± 2.31mm3 to 9.23 ± 1.38 (p = 0.0001) at the 6-month follow-up

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 (chi(2)= 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

Preoperative study of the inner segment/outer segment junction of photoreceptors by spectral-domain optical coherence tomography as a prognostic factor in patients with epiretinal membranes

Objective: to demonstrate whether the preoperative integrity of the inner segment/outer segment (IS/OS) junction of photoreceptors studied by spectral-domain optical coherence tomography (SD-OCT) is a prognostic factor in epiretinal membrane surgery. Methods: we retrospectively studied patients with an idiopathic epiretinal membrane who underwent a 23-gauge vitrectomy to remove this membrane. Best-corrected visual acuity (BCVA) and SD-OCT scans were examined before and 6 months after the surgery. We studied the retinal microstructure, especially the IS/OS junction of the photoreceptors, and evaluated the intergroup differences between patients with an intact layer and those with an irregular or disrupted layer. We applied both the Wilcoxon and Mann-Whitney tests for statistical analysis. Results: in total, 51 eyes from 51 enrolled patients were examined in this study. The postoperative BCVA was significantly better for eyes that had an intact IS/OS junction than for eyes that had an irregular or disrupted IS/OS junction, as preoperatively observed with SD-OCT scans (P < 0.001). We also observed an important association between disrupted IS/OS junctions and the presence of cystic macular edema (P < 0.01). Conclusion: the presence of an intact IS/OS junction on the preoperative SD-OCT scan was an important predictor of better visual recovery after epiretinal membrane surgery

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