[Morphological features of vasoproliferative tumor of the retina]. / Morfologicheskie osobennosti vazoproliferativnoi opukholi setchatki.

Vasoproliferative retinal tumor (VPT) is a term proposed by ophthalmologists in relation to the totality of manifestations of an intraocular volumetric process with involvement of the inner lining of the eye, an integral part of which is the active growth of blood vessels. The available literature data on the morphology of this process are very contradictory and ambiguous. The article presents two clinical cases of vasoproliferative retinal tumor with own illustration of morphological studies.

Benign Lobular Inner Nuclear Layer Proliferations of the Retina Associated with Congenital Hypertrophy of the Retinal Pigment Epithelium.

PURPOSE: To report the clinical and imaging findings of 4 patients with benign intraretinal tumors, 2 of which were associated with retinal pigment epithelium (RPE) hypertrophy. To our knowledge, this condition has not been described previously and should be distinguished from retinoblastoma and other malignant retinal neoplasms. DESIGN: Retrospective case series. PARTICIPANTS: Four patients from 3 institutions. METHODS: Four patients with intraretinal tumors of the inner nuclear layer (INL) underwent a combination of ophthalmic examination, fundus photography, fluorescein angiography, OCT, OCT angiography, and whole exome sequencing. MAIN OUTCOME MEASURES: Description of multimodal imaging findings and systemic findings from 4 patients with benign intraretinal tumors and whole exome studies from 3 patients. RESULTS: Six eyes of 4 patients 5, 13, 32, and 27 years of age were found to have white intraretinal tumors that remained stable over the follow-up period (range, 9 months-4 years). The tumors were unilateral in 2 patients and bilateral in 2 patients. The tumors were white, centered on the posterior pole, and multifocal, with some consisting of multiple lobules with arching extensions that extended beyond the central tumor mass. OCT demonstrated these lesions to be centered within the INL at the border of the inner plexiform layer. In addition, 2 patients demonstrated congenital hypertrophy of the RPE (CHRPE) lesions. Three of 4 patients underwent whole exome sequencing of the blood that revealed no candidate variants that plausibly could account for the phenotype. CONCLUSIONS: We characterize a novel benign tumor of the INL that, in 2 patients, was associated with separate CHRPE lesions. We propose the term benign lobular inner nuclear layer proliferation to describe these lesions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Advancing retinoblastoma detection based on binary arithmetic optimization and integrated features.

Retinoblastoma, the most prevalent pediatric intraocular malignancy, can cause vision loss in children and adults worldwide. Adults may develop uveal melanoma. It is a hazardous tumor that can expand swiftly and destroy the eye and surrounding tissue. Thus, early retinoblastoma screening in children is essential. This work isolated retinal tumor cells, which is its main contribution. Tumors were also staged and subtyped. The methods let ophthalmologists discover and forecast retinoblastoma malignancy early. The approach may prevent blindness in infants and adults. Experts in ophthalmology now have more tools because of their disposal and the revolution in deep learning techniques. There are three stages to the suggested approach, and they are pre-processing, segmenting, and classification. The tumor is isolated and labeled on the base picture using various image processing techniques in this approach. Median filtering is initially used to smooth the pictures. The suggested method's unique selling point is the incorporation of fused features, which result from combining those produced using deep learning models (DL) such as EfficientNet and CNN with those obtained by more conventional handmade feature extraction methods. Feature selection (FS) is carried out to enhance the performance of the suggested system further. Here, we present BAOA-S and BAOA-V, two binary variations of the newly introduced Arithmetic Optimization Algorithm (AOA), to perform feature selection. The malignancy and the tumor cells are categorized once they have been segmented. The suggested optimization method enhances the algorithm's parameters, making it well-suited to multimodal pictures taken with varying illness configurations. The proposed system raises the methods' accuracy, sensitivity, and specificity to 100, 99, and 99 percent, respectively. The proposed method is the most effective option and a viable alternative to existing solutions in the market.

Comparative Study of Ultrasonography and Ultra-Widefield Fundus Photographs for Measurements of the Diameter of Choroidal and Retinal Tumors.

INTRODUCTION: Measurement of the largest basal dimension (LBD) of intraocular tumors is important as a prognostic parameter. To evaluate the potential value of true color ultra-widefield fundus photography for measuring tumors, we compared LBD measurements of choroidal and retinal tumors using a color ultra-widefield fundus camera with clinical estimation based on indirect ophthalmoscopy and standardized ophthalmic ultrasound. METHODS: The LBD of 148 choroidal and retinal tumors in 148 patients seen at Tongren Hospital were measured using ultra-widefield fundus photography and compared with measurements obtained using B-scan ultrasonography and clinical estimates based on indirect ophthalmoscopy. RESULTS: Paired t-tests and Bland-Altman plots reveal that measurements from ultra-widefield fundus photographic images are not statistically different from clinical estimates and ultrasound measurements. The results also showed that, although not statistically significant, when the tumor boundary was clear, the height was < 3 mm, or the tumor was pigmented, measurement from ultra-widefield fundus photography tended to be greater than those obtained by ultrasound. CONCLUSIONS: The LBD measurement using ultra-widefield fundus photography correlated well with ultrasonography and clinical estimation and could be used as a reliable tool for measuring the LBD of choroidal and retinal tumors.

Noninvasive Imaging of a Vasoproliferative Retinal Tumor Treated with Cryopexy.

Optical coherence tomographic angiography (OCTA) has emerged as a rapid, noninvasive imaging modality to visualize the vascular networks in the retina and choroid. Here, we report the clinical findings in a case of primary vasoproliferative retinal tumor (VPRT) observed by the wide-field swept-source OCTA. A 74-year-old male patient with central vision loss and metamorphopsia in his left eye was referred to our hospital. At the first visit, the best-corrected visual acuity was 20/20 OD and 20/40 OS. Fundus examination revealed the presence of the epiretinal membrane and inferotemporal reddish retinal tumor in the left eye. Fluorescein angiography and indocyanine green angiography (ICGA) showed leaky characteristics and sharply defined structure of vessels in the retinal tumor, respectively. The patient was diagnosed with the VPRT with secondary epiretinal membrane and underwent pars plana vitrectomy with internal limiting membrane peeling, retinal photocoagulation, and triple freeze and thaw procedure using cryopexy. Whereas wide-field swept-source OCTA preoperatively depicted the flow signals as distinctive vascular structures similar to ICGA, the tumor color turned out to be ischemic white, and the flow signals detected by wide-field OCTA disappeared after the surgery, indicating that the freezing effect of transscleral cryopexy sufficiently reached the surface of the tumor. In sum, wide-field swept-source OCTA is a useful imaging modality that can be noninvasively and repetitively performed to determine the treatment effect in cases of peripheral retinal tumors such as VPRT.

Pseudoangiomatous retinal gliosis (PARG) treated with iodine plaque in patient with chronic retinal detachment.

Purpose: To describe a case of a chronic retinal detachment complicated by the development of pre and subretinal hemorrhage secondary to a large pseudoangiomatous retinal gliosis (PARG) that interfered with retinal reattachment. After the lesion was regressed following plaque radiotherapy retinal reattachment was successfully completed. Observations: A 56y.o healthy man with known history of a chronic inferior rhegmatogenous retinal detachment (RD) of the left eye (OS) presented to the Bascom Palmer Eye Institute (BPEI) emergency department (ED) complaining of new floaters OS. On examination, the patient had a visual acuity of 20/30 right eye (OD) and 20/200 OS. Fundoscopic examination showed a treated tear in OD and dense vitreous hemorrhage OS. Initial B-scan ultrasonography OS showed an inferior RD with diffuse hyperechoic material in the vitreous cavity, preretinal and subretinal space most consistent with hemorrhage. Three days later the patient presented with further vision loss and a repeat B scan showed total RD and increasing subretinal hemorrhage with a solid mass like lesion. At this point, decision was made to proceed with retinal detachment repair, removal of the vitreous hemorrhage, and retina evaluation. During surgery, a total retinal detachment was encountered with poor view of the inferior retina due to a large round vascular lesion in the subretinal space with surrounding hemorrhage and clots. The retina was reattached during surgery, however, the postop was complicated by recurrence of VH, dense hyphema, increased IOP, recurrence of retinal detachment, and growth of the mass like lesion noted during surgery. Consultation with ocular oncology diagnosed the patient with secondary PARG lesion and plaque radiotherapy was given achieving remarkable regression of the lesion. After the lesion had regressed, successful retinal reattachment was achieved, and the patient had excellent visual recovery. Conclusion and importance: PARG lesions are uncommon in particular when associated to chronic retinal detachments. This case highlights the importance of having a high clinical suspicion for the development of these lesions to diagnose them correctly and treat them aggressively with plaque radiotherapy in order to be able to manage the underlying complex retinal detachment.

Zebrafish as an Orthotopic Tumor Model for Retinoblastoma Mimicking Routes of Human Metastasis.

BACKGROUND: Retinoblastoma (RB) is the most common eye cancer in children that has a high mortality rate when left untreated. Mouse models for retinoblastoma have been established but are time- and cost-intensive. The aim of this work was to evaluate an orthotopic transplantation model of retinoblastoma in zebrafish that also allows for tracking migratory routes and to explore advantages and disadvantages with respect to drug testing. METHODS: Three fluorescence-labeled retinoblastoma cell lines (RB355, WERI-RB-1, Y79) were injected into the left eye of two-day-old zebrafish, while the un-injected right eye served as control. The migratory trajectories of injected retinoblastoma cells were observed until 8 days post injection (dpi), both in lateral and dorsal view, and measuring fluorescence intensity of injected cells was done for RB355 cells. RESULTS: Time until the onset of migration and routes for all three retinoblastoma cell lines were comparable and resulted in migration into the brain and ventricles of the forebrain, midbrain and hindbrain. Involvement of the optic nerve was observed in 10% of injections with the RB355 cell line, 15% with Y79 cells and 5% with WERI-RB-1 cells. Fluorescence intensity of injected RB355 cells showed an initial increase until five dpi, but then decreased with high variability until the end of observation. CONCLUSION: The zebrafish eye is well suited for the analysis of migratory routes in retinoblastoma and closely mirrors patterns of retinoblastoma metastases in humans.

Indocyanine green angiographic findings in seven eyes with vasoproliferative retinal tumor.

PURPOSE: Vasoproliferative tumors (VPTs) are rare benign tumors, and detailed indocyanine green angiographic (ICGA) findings in eyes with VPTs have not been reported. We present the characteristic ICGA findings in seven eyes with a VPT. OBSERVATIONS: We present the fluorescein angiographic (FA) and ICGA findings of seven consecutive patients who were diagnosed with primary VPT from April 2013 to March 2015 in the Oncology Service of the Department of Ophthalmology, Tokyo Medical and Dental University. We reviewed the demographics of the seven patients with VPTs. Abnormal vessels within the tumor were observed in three cases with active tumors. These vessels were hypofluorescent in the ICGA images in the scar phase. On the other hand, three cases in which the exudation remained from the initial visit to the last examination had abnormal vessels in the ICGA images. The remaining case had one straight vessel in the tumor from the initial to the last examination in the scar phase. FA in the active phase changed from hyperfluorescent leakage to staining in one eye, and the remaining six eyes continued to show hyperfluorescent leakage throughout the examination period. CONCLUSIONS: The leakage of fluorescein continued from the initial to the final examination even after the activity of the tumor had decreased. In the active phase, ICGA showed abnormal vessels with or without leakage, and the tumors at the scar phase show a hypofluorescent lesion. IMPORTANCE: ICGA supported the ophthalmoscopic findings, and can be used as a diagnostic aid to confirm a regression of the VPTs.

Optic nerve head reactive retinal astrocytic tumor treated with photodynamic therapy.

PURPOSE: To describe the unusual presentation and the treatment course of a case of bilateral optic nerve head reactive retinal astrocytic tumor (RRAT). OBSERVATIONS: A 29 year-old woman with bilateral optic disc masses presented with declining vision refractory to anti-vascular endothelial growth factor (VEGF) injections. After total loss of vision in her left eye, diagnostic enucleation and histopathology was consistent with RRAT. Staged photodynamic therapy (PDT) treatments over a period of four months in the better seeing eye resulted in stabilization of vision, improvement in intraretinal and subretinal fluid, and shrinkage of the optic disc mass. CONCLUSIONS: In this unusual case of bilateral vision-threatening optic nerve head RRAT that were refractory to multiple therapies including anti-VEGF injections, PDT demonstrated safety and efficacy. Diagnostic work-up included whole exome sequencing (WES) that was negative for mutations in genes related to von-Hippel-Lindau (VHL), neurofibromatosis, tuberous sclerosis, and hypoxia-inducible factor (HIF)-2 α .

Retinal anaplastic pleomorphic xanthoastrocytoma unassociated with phakomatosis.

PURPOSE: To present a rare anaplastic form of retinal pleomorphic xanthoastrocytoma (PXA) unassociated with phakomatosis. METHODS: A 9-year-old girl, presented with a rapidly growing unilateral intraocular white mass unresponsive to intra-arterial chemotherapy, underwent enucleation with the clinical suspicion of retinoblastoma versus malignant astrocytoma. RESULTS: Histopathology revealed pleomorphic cells with rosenthal fibers, mitosis, and necrosis. Immunohistochemistry confirmed the diagnosis of anaplastic pleomorphic xanthoastrocytoma (aPXA). The patient had no signs of phakomatosis. CONCLUSION: Retinal PXA may occur in patients without phakomatosis and rarely progress toward malignant transformation.

So-called massive retinal gliosis: A critical review and reappraisal.

Massive retinal gliosis, a nonneoplastic retinal glial proliferation, was first described in detail over 25 years ago, before the era of immunohistochemistry, in a series of 38 cases-to which can be added 30 case reports or small series (no more than 3 cases) subsequently. We analyze a new series of 3 nontumoral intraretinal glioses and 15 cases of tumoral retinal gliosis, not all of which, strictly speaking, were massive. The data from this series are compared with the findings in previously published cases. Included are 2 cases of massive retinal gliosis diagnosed from evisceration specimens. In reviewing all published and current cases, we were able to establish 3 subgroups of retinal tumoral glioses rather than a single "massive" category: focal nodular gliosis, submassive gliosis, and massive gliosis. Among 43 reported cases, including the present series, but excluding the previous large series of 38 cases in which substantial clinical data were omitted, there were 19 men and 24 women. Their mean and median ages were 36.2 years and 36 years, respectively, with a range of 2 to 79 years. All lesions were composed of mitotically quiet, compact spindled fibrous astrocytes devoid of an Alcian blue-positive myxoid matrix. The most common associated ocular conditions were phthisis bulbi and congenital diseases or malformations. Histopathologically, all 3 tumoral categories were accompanied by progressively more extensive fibrous and osseous metaplasia of the pigment epithelium, the latter forming a clinically and diagnostically useful, almost continuous, outer rim of eggshell calcification in the submassive and massive categories that should be detectable with appropriate imaging studies. In decreasing order of frequency, microcysts and macrocysts, vascular sclerosis, exudates, calcospherites, and Rosenthal fibers were observed among the proliferating fibrous astrocytes. Immunohistochemistry was positive for glial fibrillary acidic protein in all cases and nestin in most (an intermediate cytoplasmic filament typically restricted to embryonic and reparative neural tissue). The nonneoplastic nature of all categories of gliosis was confirmed by absent TP53 (tumor suppressor gene) dysregulation, Ki-67 negativity, and intact p16 expression (the protein product of the p16 tumor suppressor gene) in the overwhelming majority of cases. These findings indicate an intrinsic attempt to regulate and maintain a low level of glial cell proliferation that becomes unsuccessful as the disease evolves. The categories of tumoral proliferation appeared to constitute a spectrum. We conclude that focal nodular tumors encompass lesions previously called retinal vasoproliferative lesions, which display the same histopathologic and immunohistochemical findings as 3 major categories of retinal gliosis characterized herein.