Angiogenesis is a critical player in tumor metastasis that is involved in the pathophysiology of the pediatric ocular cancer retinoblastoma (RB). This review summarizes evidence linking angiogenesis to RB prognostication, response to treatment, and therapy. Vascular endothelial growth factor (VEGF), a major proangiogenic growth factor, has potential as a biomarker of therapy response in RB treatment. High VEGF correlates with poor chemotherapy response, subsequent local invasion, and lower patient survival. VEGF levels are also strongly correlated with choroidal invasion, poor differentiation, and an overall negative disease prognosis for RB patients. In contrast, decreasing VEGF levels can predict vitreous seed regression after intravitreal chemotherapy. Further investigation is needed to determine the accuracy and clinical value of using aqueous humor liquid biopsies to assess VEGF levels to predict prognosis or therapy response. Antiangiogenic agents, including approved drugs and experimental compounds, have shown potential in RB models and may become potential therapeutics, adjuvants to current chemotherapies, or treatments for chemotherapy complications, although there is limited evidence that antiangiogenic monotherapy may be sufficient for RB. Overall, future research aimed at integrating angiogenesis markers and therapies with existing RB strategies holds promise for improving patient outcomes and personalizing treatment approaches.

The addition of immune checkpoint inhibitors (ICIs), especially PD-1 inhibitors, as a treatment option for patients with locally advanced or metastatic periocular squamous cell carcinoma (SCC) with orbital invasion or perineural spread (PNS) is a major advance. In the case of patients with locally advanced periocular SCC with orbital invasion, ICIs can result in significant tumor shrinkage and potential avoidance of orbital exenteration or other radical surgery. In the case of SCC with PNS, using PD-1 inhibitors, as an alternative to high-dose orbital radiation therapy, is effective and can prevent vision loss and ocular toxicity from radiation. For conjunctival SCC, PD-1 inhibitors can result in tumor shrinkage in patients with high tumor mutation burden.

Intra-arterial chemotherapy (IAC) has emerged as a standard of care for retinoblastoma (RB). Our study evaluates the outcomes, adverse effects and challenges of IAC in the management of RB in an Indian cohort. This retrospective study analyzed 20 patients (n=21 eyes) with RB treated with IAC at a single tertiary center. Drugs used were melphalan (5/7.5mg) and topotecan (1/2mg) (n=14) or melphalan (5mg) alone (n=3) or triple therapy, which included carboplatin (30mg) along with these drugs (n=4). Patient demographics, clinical staging, globe salvage rates, tumor regression, adverse effects, and challenges were assessed. Eyes were classified according to ICRB as group B (n=5), C (n=1), D (n=7), and E (n=8). Of the 21 eyes treated, successful globe salvage was achieved in 81% of the cases, with a median follow-up of 20 months. Complete regression of the main tumor was seen in 12 eyes (57%) and partial regression in 9 eyes (43%). Among adverse effects, vitreous hemorrhage (n=3), rhegmatogenous retinal detachment (n=3), choroidal ischemia (n=1), isolated subretinal hemorrhage (n=2), retinal pigment epithelium degeneration (n=3), ophthalmic artery stenosis (n=2), occlusive vasculitis (n=1), forehead pigmentation in 1 patient, 1 had third nerve palsy with complete ptosis and 1 had 30-degree exotropia. IAC is an effective treatment modality for RB, achieving high globe salvage rates, but parallelly, the adverse effects associated with IAC should be kept in mind. This study provides critical insights into the real-world application of IAC in resource-limited settings, highlighting both its promise and limitations.

In eyes with retinal hemangioblastomas (RH), vision loss may occur despite treatment due to recurrent macular edema, macular pucker, vitreous hemorrhage, and exudative, tractional, or combined retinal detachment. Pars plana vitrectomy (PPV) plays a critical role in managing these complications. This review aims to evaluate the outcomes of PPV in patients with RH. We searched PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Google Scholar, and Web of Science (2000 to 2025) using the keywords "retinal hemangioblastoma," "capillary hemangioblastoma," "von Hippel-Lindau retina," combined with "vitrectomy," or "pars plana vitrectomy." Given the rarity of the condition, retrospective case series were included if they had ≥4 cases. Single anecdotes and non-English articles were excluded. Two independent reviewers evaluated the studies for qualitative and quantitative synthesis. Our search yielded 120 results, of which eight studies published between 2011 and 2024 met the inclusion criteria. All were retrospective case series (level IV evidence). A total of 107 eyes from 102 patients were analyzed, with sample sizes ranging from 4 to 23 eyes. Anatomic success, defined as retinal reattachment, ranged from 70% to 100% by final follow-up. However, many eyes remained in the low vision range despite anatomic success. New tumor development and proliferative vitreoretinopathy (PVR)-related complications remain key challenges in long-term management. While the evidence is limited due to study design and sample size, consistent trends across the literature suggest PPV is anatomically effective, though visual outcomes remain guarded.

Conjunctival melanoma is a rare, potentially lethal cancer that mainly affects fair-skinned individuals. The tumor mostly arises from primary acquired melanosis (PAM) with atypia. The presentation of conjunctival melanoma varies and should be clinically differentiated from an array of ocular surface pigmented and nonpigmented lesions. Mutations in the oncogenes BRAF (V600E) and NRAS, and the tumor suppressor gene NF1, are associated with worse survival. UV signature mutations are frequently observed in the bulbar conjunctival melanoma. The TNM staging classifies conjunctival melanoma according to its location and extent. The treatment of conjunctival melanoma depends on tumor staging. Surgical excision of a localized bulbar or forniceal tumor with the no-tumor-touch technique and margin cryotherapy can be sufficient for local control. Adjunctive radiotherapy options include Proton beam radiotherapy, Plaque radiotherapy for ocular surface melanoma, Orthovoltage (Deep x-ray) radiotherapy for palpebral melanoma, and Megavoltage LINAC-based photon radiotherapy can be used for locally invasive and localized orbital extension of conjunctival melanoma. Topical mitomycin-C eye drops are used for diffuse flat melanoma or PAM with severe atypia. Systemic targeted therapy such as BRAF inhibitors for melanoma with BRAF mutation, and systemic immunotherapy drugs have been recently used for more extensive or metastatic disease. Risk factors for metastasis include: greater tumor thickness, non-bulbar location, low tumor pigmentation, histologic ulceration, >1 mitotic figure per mm2, and adjacent structures invasion. Localized tumors should be excised en block, and incisional biopsy should be avoided, which could lead to local widespread tumor dissemination and subsequent recurrence and metastasis.

Management of retinoblastoma has evolved drastically with the advent of targeted chemotherapy, such as intra-arterial chemotherapy, intravitreal chemotherapy, and intracameral chemotherapy. Intravitreal chemotherapy has emerged as the frontline therapy for the management of vitreous seeding. It has also shown beneficial effects on subretinal seeding, the 2 major therapeutic challenges for globe salvage in retinoblastoma. The enhanced efficacy and safety of current intravitreal agents have led to improved globe and vision salvage, resulting in better survival outcomes. The authors discuss current trends, indications, and practice patterns of intravitreal chemotherapy for retinoblastoma, highlighting potential groundbreaking advancements, including the role of nanoparticle technology.

Solitary fibrous tumors (SFTs) of the orbit are rare mesenchymal neoplasms that typically exhibit indolent behavior. However, a subset may recur, sometimes many years after initial treatment, posing significant diagnostic and therapeutic challenges. Because of the rarity of recurrent orbital SFTs, there is limited literature addressing their clinicopathologic features, diagnostic evolution, and optimal management strategies. This study aims to analyse the clinical, radiologic, histopathologic, and immunohistochemical characteristics of 4 patients with recurrent orbital SFTs and to compare these findings with existing literature to elucidate prognostic factors and guide long-term management. We retrospectively reviewed the clinical records of 4 patients with histologically confirmed recurrent orbital SFTs treated at our institution. Data regarding initial presentation, radiologic characteristics, histopathology, time to recurrence, mitotic activity, Ki-67 index, necrosis, and immunohistochemical profile were collected. All cases were evaluated for nuclear STAT6 expression, CD34 positivity, and proliferation index. A comparative review of previously published cases of recurrent orbital SFTs was conducted through the PubMed database. The recurrence interval ranged from 6 to 15 years. Initial diagnoses in 3 of the 4 cases were incorrect (hemangiopericytoma, Schwannoma, and cellular SFT), and were revised upon recurrence using updated immunohistochemistry. All cases demonstrated strong nuclear STAT6 and CD34 positivity on recurrence. Mitotic indices ranged from 0 to 10 per 10 high-power fields, and Ki-67 indices ranged from 2% to 40%. Necrosis was observed in one case only. Two patients required eyelid-sparing exenteration, whereas the others were managed with wide excision and orbital floor reconstruction. All patients remained recurrence-free at 2 to 3 years post-re-excision. Recurrent orbital SFTs can present after a prolonged latency and may exhibit histologic evolution or diagnostic misclassification at initial presentation. Accurate diagnosis requires integration of histopathology with STAT6-based immunohistochemistry. Ki-67 and mitotic indices alone may not predict recurrence risk. Complete surgical excision remains the cornerstone of effective management. Our findings emphasize the importance of long-term surveillance and re-evaluation in cases with uncertain or evolving histopathologic features.

Retinoblastoma is considered a prototype pediatric malignancy as retinoblastoma research has been instrumental in advancing our knowledge of cancer genetics, tumor suppressor genes, and the development of new treatment approaches. Also, retinoblastoma boasts one of the highest survival rates among pediatric cancers, with survival rates often exceeding 90% in developed countries. The research focus is shifting towards improved globe and vision salvage. Also, there is emphasis on advancing treatments that are tailored based on individual patient characteristics, including tumor genetics and molecular markers, to improve outcomes and minimize side effects.

To describe a case series of Coats disease with macular nodule mimicking retinoblastoma. Retrospective case series. Of 339 patients with Coats disease, 7 (2%) with macular nodules were included. All had a referral diagnosis of retinoblastoma. All were males (mean age-6y). The most common presenting complaint was decreased vision (n=4, 57%). Median best corrected visual acuity at presentation was counting fingers close to face, which was maintained at last follow-up (mean, 8 months). The nodule had a mean diameter of 5x4x3mm, was grayish white, and bilobed (n=3, 43%), or dome shaped (n=4, 57%) with surface pigmentation (n=4, 57%), involving fovea (n=5, 71%), with surrounding exudates and second- or third-order retinal vessels. OCT (n=4) showed a well-defined hyperreflective subretinal nodule with posterior shadowing, cysts, and exudates. USG (n=6) showed an echodense intraocular nodule with moderate internal reflectivity with hyperechoic foci in 2 (33%) cases. FFA showed early- and mid-phase hypo-fluorescence with focal leakage with late-phase hyperfluorescence. Focal green laser photocoagulation of the telangiectatic vessels was performed in 5, one underwent subretinal fluid drainage and scleral buckling, and one was observed. Macular nodule in Coats disease represents a preferential accumulation of lipid in the macula. This rare variant of Coats disease can mimic retinoblastoma process. Be aware of this entity to ensure appropriate diagnosis and treatment.

Rare pediatric eye cancers (R-PECs) encompass over 30 benign and malignant neoplasms affecting various ocular structures. Despite their potential for severe morbidity and mortality, many R-PECs remain poorly understood due to their rarity, clinical heterogeneity, and the limited availability of high-quality biospecimens. The historic example of retinoblastoma illustrates how access to well-annotated tumor tissue enabled groundbreaking discoveries, including the identification of the RB1 gene and MYCN-amplified retinoblastoma. However, a lack of centralized, high-quality resources continues to hinder progress across the spectrum of R-PECs. Biobanking offers a solution by systematically collecting, storing, and sharing biospecimens and data under standardized protocols and formal governance. Pediatric biobanks face unique ethical and operational challenges, including obtaining dynamic consent and safeguarding participant autonomy. Yet, they also offer unique opportunities, including the creation of renewable models (eg,. organoids, cell lines) and the integration of imaging and multiomics data. This review highlights these opportunities and challenges, drawing on insights from the Kids Eye Biobank. Through structured resource collection, governance, and patient engagement, the Kids Eye Biobank demonstrates how biobanking can transform R-PEC research and accelerate discovery in this underserved area.