[Circumscribed choroidal hemangioma and non-pigmented choroidal melanoma: clinical, instrumental and molecular genetic features]. / Otgranichennaya gemangioma i bespigmentnaya melanoma khorioidei: kliniko-instrumental'nye i molekulyarno-geneticheskie osobennosti.

Circumscribed choroidal hemangioma (CCH) and early non-pigmented choroidal melanoma (CM) have similar clinical, ultrasound and morphometric features, which in some cases makes their differential diagnosis difficult. There are few studies in the literature devoted to a comparative analysis of the molecular genetic features of CCH and non-pigmented CM, and the results of those studies are contradictory. PURPOSE: This study attempts to develop a method of non-invasive molecular genetic differential diagnostics of CCH and non-pigmented CM. MATERIAL AND METHODS: Based on the results of clinical and instrumental examination methods, 60 patients (60 eyes) with CCH (n=30) and non-pigmented CM (n=30) were included in this prospective study. The control group consisted of 30 individuals without intraocular tumors. Mutations in the GNAQ/GNA11 genes were determined by real-time PCR using the analysis of genomic circulating tumor DNA isolated from peripheral blood plasma. The average follow-up period was 12.1±1.8 months. RESULTS: The study revealed a significant association of mutations in exons 4 and 5 of the GNAQ/GNA11 genes with the presence of non-pigmented CM (27/30; 90%). These mutations were not detected in the group of patients with CCH. Mutations in exons 4 and 5 of the GNAQ/GNA11 genes were also not detected in the control group of healthy individuals. CONCLUSION: This study proposes a method of non-invasive and low-cost differential diagnostics based on molecular genetic analysis and detection of mutations in exons 4 and 5 of the GNAQ and GNA11 genes, which are specific for CM (90%).

[Predicting the effectiveness of organ-preserving treatment of choroidal melanoma using optical coherence tomography data]. / Prognozirovanie effektivnosti organosokhrannogo lecheniya melanomy khorioidei po dannym opticheskoi kogerentnoi tomografii.

Optical coherence tomography (OCT) is currently widely used for the diagnosis of choroidal melanoma (CM), but the problem of predicting the outcomes of planned CM treatment remains unsolved. PURPOSE: This study was conducted to identify OCT signs that adversely affect the outcome of organ-preserving CM treatment. MATERIAL AND METHODS: OCT scan images of 30 patients who underwent organ-preserving treatment and were under observation were selected for this study. Brachytherapy (BT) as monotherapy was performed in 27 patients (in 2 cases - twice, and in 1 case - three times), in one patient - in combination with the previous transpupillary thermotherapy (TTT). Multiple TTT (4 sessions within 4 months) as monotherapy were performed in 2 patients. In 9 cases, a single organ-preserving treatment (BT - 6 patients, TTT - 3 patients) was ineffective. In these cases, the effectiveness of the first stage of organ-preserving treatment was taken into account. RESULTS: Seven signs of an unfavorable prognosis of the performed treatment were identified by analyzis of tomograms and statistical processing of the obtained data. These signs include: the presence of intraretinal edema, detachment of the neuroepithelium (NED) over the tumor, including with a break in the photoreceptors, accumulation of transudate over the tumor, the presence of large cysts, intraretinal cavities and NED near the tumor (secondary retinal detachment). A combination of three or more signs were observed in all cases of inefficiency of the first stage of treatment. Most often, intraretinal edema and NED over the tumor were combined with the accumulation of subretinal transudate and NED near the tumor. The presence of 6 or all 7 signs took place in cases of a negative therapeutic effect after local destruction. CONCLUSION: When planning organ-preserving CM treatment, in addition to biometric parameters, it is necessary to pay special attention to the identification of such morphological signs as NED over and near the tumor, accumulation of transudate under the NED, the presence of intraretinal edema, large intraretinal cysts and cavities.

Unusual Presentation of Unilateral Choroidal Melanoma with Bilateral Vasculitis in Young Individual: A Case Report and Review of Literature.

Ocular melanoma stands as the predominant primary intraocular malignancy, albeit infrequently exhibiting ipsilateral inflammatory manifestations. In this article, we present an exceptional case involving a middle-aged male who presented with unilateral ocular choroidal melanoma alongside bilateral retinal vasculitis. The patient initially received temporary steroid treatment, followed by brachytherapy, which contributed to the resolution of vasculitis symptoms. The study aims to document the atypical occurrence of bilateral retinal vasculitis, which could potentially masquerade as melanoma, emphasizing the need for heightened vigilance and further investigations when encountering choroidal masses in its presence. Future research endeavors are warranted to better understand the incidence of such occurrences in this context.

A Case Series of Choroidal and Orbital Neuroendocrine Tumors: Metastasis: Two Patients Treated With Peptide Radionuclide Therapy.

ABSTRACT: Neuroendocrine tumors (NETs) are rare cancers with heterogeneous histologies, response to treatments, and prognoses. Majority of these cancers originate in the gastrointestinal tract and metastasize to the liver. We report the cases of 5 patients with low-grade NET disease with rare metastases to the choroids. Two of the patients were treated with peptide receptor radionuclide therapy (lutetium 177 [ 177 Lu]). This is the first report confirming peptide radionuclide therapy safety in patients with low-grade NET with ocular metastases.

Multispectral Fundus Photography of Choroidal Nevi With Trans-Palpebral Illumination.

Purpose: The purpose of this study was to investigate the spectral characteristics of choroidal nevi and assess the feasibility of quantifying the basal diameter of choroidal nevi using multispectral fundus images captured with trans-palpebral illumination. Methods: The study used a widefield fundus camera with multispectral (625 nm, 780 nm, 850 nm, and 970 nm) trans-palpebral illumination to examine eight subjects diagnosed with choroidal nevi. Geometric features of nevi, including border clarity, overlying drusen, and lesion basal diameter, were characterized. Clinical imagers, including scanning laser ophthalmoscopy (SLO), autofluorescence (AF), and optical coherence tomography (OCT), were utilized for comparative assessment. Results: Fundus images depicted nevi as dark regions with high contrast against the background. Near-infrared (NIR) fundus images provided enhanced visibility of lesion borders compared to visible fundus images and SLO images. Lesion-background contrast measurements revealed 635 nm SLO at 11% and 625 nm fundus at 42%. Significantly enhanced contrasts were observed in NIR fundus images at 780 nm (73%), 850 nm (63%), and 970 nm (67%). For quantifying the diameter of nevi, NIR fundus images at 780 nm and 850 nm yielded a deviation of less than 10% when compared to OCT measurements. Conclusions: NIR fundus photography with trans-palpebral illumination enhances nevi visibility and boundary definition compared to SLO. Agreement in diameter measurements with OCT validates the accuracy and reliability of this method for choroidal nevi assessment. Translational Relevance: Multispectral fundus imaging with trans-palpebral illumination improves choroidal nevi visibility and accurately measures basal diameter, promising to enhance clinical practices in screening, diagnosis, and monitoring of choroidal nevi.

Bilateral choroidal osteoma: long-term follow-up of secondary choroidal neovascularization in a child using antiangiogenic therapy.

Choroidal osteoma is a rare condition, and its treatment is not well established, especially in the pediatric population, where use of antiangiogenics for choroidal neovascularization is poorly studied. Few studies have reported the long-term follow-up of pediatric patients with bilateral choroidal osteomas. We report the case of a girl who was diagnosed at the age of 3, with the appearance of bilateral secondary choroidal neovascularization, and has been under strict observation for 12 years. The effectiveness of antiangiogenic agents as a long-term therapeutic option for secondary choroidal neovascularization in pediatric patients with symptomatic choroidal osteomas is discussed.

Intraocular schwannoma: case series of 28 patients and literature review.

PURPOSE: Intraocular schwannoma is a rare tumour, which is often misdiagnosed. We presented the demographics and clinical characteristics of patients with intraocular schwannoma. METHODS: Retrospective case series were collected between May 2005 and July 2021 in Beijing Tongren Hospital. RESULTS: A total of 28 patients were diagnosed with intraocular schwannoma on histopathological examination of surgical specimen. The median age was 39 years (range: 12-64). Fourteen patients were female and 14 were male. Among the all subjects, 21/28 patients (75.0%) presented as visual loss, and 3/28 patients (10.7%) had visual field loss. Intraocular schwannoma presented as nonpigmented mass in the ciliary body in 12/28 cases (42.9%), in the choroid in 9/28 cases (32.1%), and in ciliochoroid in 7/28 cases (25.0%). Intraocular schwannoma was often clinically misdiagnosed as uveal melanoma, which occurred in 16/28 patients (57.1%). Tumour excision with pars plana vitrectomy was performed for all included patients. Endoresection with lens removal was performed for tumours in the choroid, while transscleral resection was performed for tumours located in ciliary body or ciliochoroid. Increased light transmission was detected in 12/28 cases (42.9%). In the consecutive follow-up (median: 73 months, range: 7-193 months), no cases of recurrence or metastatic disease were detected. CONCLUSIONS: Intraocular schwannoma is a rare benign tumour. It usually presents as nonpigmented mass, which can easily be misdiagnosed as nonpigmented uveal melanoma.

Disinsert, retract and rotate technique of plaque brachytherapy.

BACKGROUND: Plaque brachytherapy is commonly used in the management of choroidal melanomas. The surgical steps usually involve creating a conjunctival peritomy, fixing the recti muscles, with or without disinserting them based on the location of the lesion, and placing the plaque. The inferior oblique muscle is attached close to the macula, and in cases of perimacular or peripapillary lesions, the muscle needs to be sacrificed. PURPOSE: The authors here demonstrate a novel technique of placing radioactive plaque without disinserting the inferior oblique muscle in cases of perimacular or peripapillary choroidal melanomas. SYNOPSIS: The video demonstrates how the "disinsert, retract, and rotate technique" of brachytherapy plaque placement can be performed and what are the fundamentals behind this technique. The authors have performed this procedure multiple times and there has been no incidence of plaque tilt or migration. HIGHLIGHTS: In perimacular and peripapillary choroidal melanoma brachytherapy plaque placement, the inferior oblique muscle can be spared. The simple technique does not lead to any tilt or migration of the radioactive plaque. VIDEO LINK: https://youtu.be/YMIg3rYyp2o.

Rhegmatogenous retinal detachment in choroidal melanoma: clinical features and surgical outcomes.

PURPOSE: To describe the clinical features, prognostic factors, safety and rate of success of surgery and visual outcomes in patients with rhegmatogenous retinal detachment (RRD) and choroidal melanoma (CM). METHODS: A retrospective, observational case-series of 21 patients with rhegmatogenous retinal detachment or combined tractional-rhegmatogenous retinal detachment in patients with choroidal melanoma over a period of 20 years. RESULTS: Nineteen patients were included in the final analysis. The mean elevation of CM was 4.0 mm and the mean largest diameter was 11.0 mm. RRD occurred after the CM treatment in 14 eyes at a mean interval of 44.2 months. The RRD was macula-on RRD in 6 eyes, there was posterior vitreous detachment (PVD) in 15 and PVR in 7 eyes. BCVA at presentation was 0.71 logMAR and final was 1.5 logMAR (p = 0.01). The primary surgical success rate was 59%. No intraocular or extraocular tumour dissemination occurred. Mean follow-up was 66 months. CONCLUSION: RRD in patients with CM is uncommon but requires multidisciplinary management. Anatomical results are favourable but visual outcomes are poor due to a combination of factors related to melanoma treatment, macular retinal detachment and PVR. Vitrectomy as a surgical intervention for RRD in treated CM appears to be safe in terms tumour dissemination.

POLYPOIDAL LESIONS ASSOCIATED WITH CHOROIDAL NEVI.

PURPOSE: To investigate eyes with polypoidal lesions associated with choroidal nevi, their multimodal imaging characteristics, and long clinical follow-up. METHODS: Multicenter, retrospective case series study of patients with polypoidal lesions overlying choroidal nevi. Demographic and clinical information were recorded. Multimodal imaging including color fundus photography, optical coherence tomography, optical coherence tomography angiography, fundus fluorescein angiography, indocyanine angiography, and A- and B-scan ultrasonography were analyzed for nevus and polypoidal lesion characteristics. RESULTS: Fourteen eyes (14 patients; mean age: 70.3 ± 6.7 years) with polypoidal lesions overlying choroidal nevi were included. The mean follow-up duration was 50.0 ± 27.9 months (range 12-108). All nevi were pigmented on color fundus photography, flat on ultrasonography with a mean basal diameter of 3.8 ± 0.4 mm. In all but one eye, optical coherence tomography showed a shallow irregular pigment epithelium detachment overlying the nevus. A total of 11/14 eyes (78.6%) had exudative activity, 9 eyes received intravitreal anti-vascular endothelial growth factor injections, and one eye required intravitreal anti-vascular endothelial growth factor combined with photodynamic therapy. Mean visual acuity was 20/32 at baseline and 20/50 at final visit. CONCLUSION: We present the largest known cohort of eyes with polypoidal lesions associated with choroidal nevi with up to 9 years follow-up. The exudative degree of the polypoidal lesion in this condition is variable and treatment decisions should be taken on an individual basis. We hypothesize that choroidal ischemia because of altered choroidal vasculature rather than Haller layer hyperpermeability plays a role in the formation of polypoidal lesions overlying nevi.

Improved Staging of Ciliary Body and Choroidal Melanomas Based on Estimation of Tumor Volume and Competing Risk Analyses.

PURPOSE: The current, 8th edition of the American Joint Committee on Cancer (AJCC) anatomic classification and staging model for uveal melanoma does not fully separate survival estimates for patients with advanced stages of the disease (e.g., IIIB and IIIC). Furthermore, some tumors in higher size categories have a smaller volume than tumors in lower categories. Therefore, we developed a novel model for prognostication of metastatic mortality based on estimations of tumor volume. DESIGN: Retrospective, multicenter case series of patients with uveal melanoma involving the choroid, ciliary body, or both. PARTICIPANTS: Six thousand five hundred twenty-eight consecutively registered patients treated at 3 tertiary ocular oncology centers on 2 continents between 1981 and 2022. METHODS: Data on survival, tumor size, and extent were collected for all 6528 patients. Tumor volume was estimated using a simple equation based on largest basal diameter and thickness. Volume-based size categories and stages were developed and validated in independent patient cohorts using competing risk analyses, and correlations with cytogenetic and cytomorphologic features were examined. MAIN OUTCOME MEASURE: Cumulative incidence of metastatic death. RESULTS: The 6528 patients were distributed over 7 stages based on estimated tumor volume and anatomic extent (V stages IA, IB, IIA, IIB, IIIA, IIIB, and IIIC), with a 15-year incidence of metastatic death ranging from 7% to 77%. A new category, V1min, and corresponding stage IA, were introduced, indicating an excellent prognosis. Metastatic mortality in V stage IIIC was significantly higher than that in V stage IIIB (P = 0.03), whereas incidence curves crossed for patients in AJCC stages IIIC vs. IIIB (P = 0.53). Univariable and multivariable competing risk regressions demonstrated higher Wald statistics for V stages compared with AJCC stages (1152 vs. 1038 and 71 vs. 17, respectively). The frequency of monosomy 3, gain of chromosome 8q, and epithelioid cytomorphologic features increased with tumor volume (R2 = 0.70, R2 = 0.50, and R2 = 0.71, respectively; P < 0.001) and showed similar correlations with both AJCC and V stages. CONCLUSIONS: Anatomic classification and staging of ciliary body and choroidal melanomas based on estimation of tumor volume improves prognostication of metastatic mortality. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Real-world experience of implementing the MOLES score in a virtual choroidal naevi clinic at a tertiary referral centre.

INTRODUCTION: The MOLES score has been validated to clinically differentiate choroidal naevi from melanomas by ocular oncologists and community optometrists. However, its utility in a virtual choroidal naevi clinic at a tertiary eye hospital without specialist ocular oncology services has not yet been evaluated. METHODS: A retrospective case review of 385 choroidal lesions in the virtual choroidal naevus clinic at Bristol Eye Hospital during January-March 2020 and April-August 2021 was performed. Choroidal lesions were assessed using the TFSOM-UHHD risk factor index and MOLES score, respectively. For both study periods, clinical outcome and adherence data were analysed. RESULTS: Choroidal lesions scored higher with the TFSOM-UHHD index (median 2) compared to the MOLES score (median 0; p < 0.001). Median required follow-up duration was 2 years for lesions assessed with the TFSOM-UHHD index, and 0 years for those graded with the MOLES score. Overall, 215 patients were appropriately discharged to community optometrists based on their MOLES score. Imaging requirements for the TFSOM-UHHD index and MOLES score protocols were met in 69.1% and 94.8% of cases, respectively. CONCLUSION: The MOLES score was easily implemented in a virtual choroidal naevus clinic, with good adherence. It increased clinic capacity by facilitating appropriate discharges of low-risk naevi to community monitoring, allowing finite and specialist hospital-based services to monitor higher-risk naevi more closely.

Central subfield thickness predicts visual acuity outcomes in plaque-irradiated eyes with choroidal melanoma.

OBJECTIVE: To determine the association between pre-operative central subfield thickness (CST) and post-radiotherapy visual acuity (VA), cystoid macular edema (CME), and intravitreal anti-vascular endothelial growth factor (VEGF) requirement. DESIGN: Single-center retrospective study. PARTICIPANTS: Patients with plaque-irradiated extramacular choroidal melanoma treated between 11/11/2011 and 4/30/2021. Pre-operative CST difference between the affected and unaffected eye was used. Kaplan-Meier analysis and hazard ratios were calculated. RESULTS: Of 85 patients, pre-operative CST was greater in the melanoma-affected eye (vs. fellow eye) by mean of 20.4 µm (median 14.0, range - 60.0-182.0). Greater CST at presentation (vs. fellow eye) was associated with larger tumor diameter (p = 0.02), greater tumor thickness (p < 0.001), and more frequent tumor-related Bruch's membrane rupture (p = 0.006). On univariate analysis of outcome data, greater CST at presentation (vs. fellow eye) was associated with higher 5-year risk (1.09 [1.02-1.17], p = 0.02) of VA 20/200 or worse and increased (1.10 [1.01-1.20], p = 0.03) likelihood for anti-VEGF injections after plaque irradiation. There was no significant association with CME. The association between CST and VA outcome remained significant on multivariate analysis accounting for impact of tumor thickness and radiation dose to optic disc, while tumor distance to fovea was the only significant factor on multivariate analysis for anti-VEGF injections. CONCLUSION: Greater CST at presentation (vs. fellow eye) was associated with worse VA outcome following plaque radiotherapy for choroidal melanoma. Large-sized tumors may contribute to a higher intraocular VEGF burden, potentially leading to greater preoperative CST, which correlates with poor VA outcome post-plaque radiotherapy.

New insights on circumscribed choroidal hemangioma: "bench to bedside".

Circumscribed choroidal hemangioma is a rare vascular hamartoma of the choroid, presenting as a red-orange mass at the posterior pole on fundoscopic examination. Despite its benign origin, associated complications such as subretinal fluid, serous retinal detachment, retinoschisis and neovascular glaucoma may lead to serious visual impairment in more than half patients. Because of its similarity to amelanotic choroidal melanoma and choroidal metastasis, differential diagnosis is still challenging for specialists. Multimodal imaging such as ultrasonography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography guides the clinician to the correct diagnosis and the proper follow-up. Treatment is indicated in symptomatic cases in order to resolve exudation and improve visual acuity. Treatment options include photocoagulation, transpupillary thermotherapy, radiation therapy, photodynamic therapy and anti-vascular endothelial growth factor therapy. Currently, photodynamic therapy is the treatment of choice due to its effectiveness and safety. The purpose of this review is to describe the latest knowledge in the etiopathogenesis of the circumscribed choroidal hemangioma, the most recent multimodal imaging findings, and the available treatment options.

PHOTODYNAMIC THERAPY-INDUCED ACUTE EXUDATIVE MACULOPATHY IN A CASE SERIES OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMA.

PURPOSE: To describe the incidence, features, and clinical outcomes of photodynamic therapy-induced acute exudative maculopathy (PAEM) in circumscribed choroidal hemangioma. METHODS: Prospective series of 10 patients who underwent standard-fluence photodynamic therapy for circumscribed choroidal hemangioma. Best-corrected visual acuity in the Early Treatment Diabetic Retinopathy Score and swept-source optical coherence tomography were performed before PDT and 3 days and 1 month after PDT. Central retinal thickness, circumscribed choroidal hemangioma retinal thickness, and subretinal fluid were measured. Photodynamic therapy-induced acute exudative maculopathy was considered as an increase ≥50 µ m in subretinal fluid or intraretinal fluid or the appearance of fibrin 3 days after photodynamic therapy. RESULTS: Six men and four women were included; median age was 55 years (19-69 years). The incidence rate of PAEM was 7 of 10. Five PAEM patients showed an increase in intraretinal fluid, two in subretinal fluid, and one developed abundant fibrin. Median best-corrected visual acuity at baseline was 57.5 letters (5-76 letters) being stable at 1 month (64 letters; 5-80) ( P = 0.03). Median central retinal thickness increased from 516 µ m (262-1,265 µ m) to 664.5 µ m after 3 days and diminished to 245 µ m after 1 month (156-1,363) ( P ≤ 0.022). In 6 of 7 of PAEM, a complete resolution of the fluid was obtained. CONCLUSION: Photodynamic therapy-induced acute exudative maculopathy was frequent in circumscribed choroidal hemangioma, although a favorable prognosis was observed in most cases.