Artificial intelligence and machine learning in ocular oncology: Retinoblastoma

Purpose: This study was done to explore the utility of artificial intelligence (AI) and machine learning in the diagnosis and grouping of intraocular retinoblastoma (iRB). Methods: It was a retrospective observational study using AI and Machine learning, Computer Vision (OpenCV). Results: Of 771 fundus images of 109 eyes, 181 images had no tumor and 590 images displayed iRB based on review by two independent ocular oncologists (with an interobserver variability of <1%). The sensitivity, specificity, positive predictive value, and negative predictive value of the trained AI model were 85%, 99%, 99.6%, and 67%, respectively. Of 109 eyes, the sensitivity, specificity, positive predictive value, and negative predictive value for detection of RB by AI model were 96%, 94%, 97%, and 91%, respectively. Of these, the eyes were normal (n = 31) or belonged to groupA (n=1), B (n=22), C (n=8), D (n=23),and E (n=24) RB based on review by two independent ocular oncologists (with an interobserver variability of 0%). The sensitivity, specificity, positive predictive value, and negative predictive value of the trained AI model were 100%, 100%, 100%, and 100% for group A; 82%, 20 21 98%, 90%, and 96% for group B; 63%, 99%, 83%, and 97% for group C; 78%, 98%, 90%, and 94% for group D, and 92%, 91%, 73%, and 98% for group E, respectively. Conclusion: Based on our study, we conclude that the AI model for iRB is highly sensitive in the detection of RB with high specificity for the classification of iRB

A short-term chick embryo in vivo xenograft model to study retinoblastoma cancer stem cells

Purpose: Cancer stem cells (CSCs) reported in various tumors play a crucial role in tumorigenesis and metastasis of retinoblastoma (Rb). Following the efforts to reduce, replace, and refine the use of mammalian models, we aimed to establish a short?term xenograft for Rb to evaluate the CSC properties of CD133? Rb Y79 cells, using the well?established chick embryo chorioallantoic membrane (CE?CAM) assay. Methods: Y79 cells were cultured, labeled with two different dyes (CM?Dil Y79 and enhanced green fluorescent protein (eGFP)) and sorted for CD133? and CD133 + subsets. Two million cells from each of the labeled groups were transplanted onto the abraded CAM on embryonic day 7 (E7). On E14, the tumor nodule formation on CAM and spontaneous metastasis to the embryos were evaluated by confocal microscopy, in vivo imaging, and histology. Results: Y79 cells formed pink–white raised perivascular nodules with feeder vessels on the CAM with both the types of labeled CD133? cells. CD133? cells, when compared to CD133 + cells, demonstrated significantly larger tumor volume (40.45 ± 7.744 mm3 vs 3.478 ± 0.69 mm3, P = 0.0014) and higher fluorescence intensity (CM?Dil: AUF = 6.37 × 107 ± 7.7 × 106 vs 1.08 × 107 ± 1.6 × 106; P < 0.0001; eGFP: AUF = 13.94 × 104 ± 2.54 × 104 vs AUF = 1.39 × 104 ± 0.4 × 104; P = 0.0003). The metastatic potential of CD133? cells was also observed to be higher as noted by in vivo imaging and histopathology. Conclusion: This study highlights that CE?CAM is a feasible alternative nonmammalian model for evaluating tumorigenicity and metastatic potential of Y79 CSCs. Increased tumorigenicity and metastatic potential of CD133? subset of tumor cells substantiate their CSC properties

Recombinant interferon alpha 2b for ocular surface squamous neoplasia: An efficient and cost‑effective treatment modality in Asian Indian patients.

Purpose: The purpose was to study the efficacy of interferon alpha 2b (INF α2b) in the treatment of ocular surface squamous neoplasia (OSSN) and analyze its cost‑effectiveness in India. Study Design: This was a retrospective study of thirty patients with OSSN treated with topical INF α2b (1 MIU/cc) ± perilesional INF α2b (5 MIU/cc). Results: The tumor involved cornea (n = 9, 30%), conjunctivo‑limbal‑corneal surface (n = 19, 63%), or bulbar conjunctiva (n = 2, 7%). The mean basal dimension of the tumor was 16 mm. The tumors belonged to Tis (n = 6, 20%) or T3 (n = 24, 80%) based on the American Joint Committee Classification, 7th edition. In the six patients with Tis, three cycles of topical INF α2b were used for immunoprevention. In the remaining 24 patients, INF α2b was advised for immunoreduction, but served as immunotherapy with 100% tumor regression in 22 (92%) cases, and resulted in 95% immunoreduction in 2 (6%) cases. Complete tumor regression by immunotherapy (n = 22) was achieved with a mean number of three topical INF α2b cycles and two perilesional injections. All these 22 patients received three additional topical INF α2b cycles after complete tumor regression. For immunoreduction (n = 2), both patients received six cycles of topical INF α2b which was three perilesional INF α2b injections. The mean total treatment cost per patient with INF α2b was INR 9164 ($US 137). Based on maximum basal diameter of tumor at presentation, the mean total treatment cost per patient with INF α2b was INR 4866 ($US 73) for eyes with microscopic evidence of tumor residue (n = 6), INR 9607 ($US 143) for tumors ≤10 mm (n = 13), and INR 10,985 ($US 164) for tumors >10 mm (n = 11), with two patients needing additional surgical excision for complete tumor control. Conclusion: INF α2b can be used for immunoreduction, immunotherapy, or immunoprevention of OSSN. INF α2b is a cost‑effective treatment modality for OSSN at an average total treatment cost of INR 9164 ($US 137) per patient.

Neoadjuvant chemotherapy for invasive squamous cell carcinoma of the conjunctiva: A case report.

A 40‑year‑old male presented with an orbital extension of conjunctival squamous cell carcinoma (SCC). The orbital mass was seen protruding outward from the left palpebral fissure overhanging the lower eyelid, completely obscuring the globe and lower lid. The patient gave a history of excision biopsy, which was histopathologically diagnosed as ocular surface squamous neoplasia. He also gave a history of tumor recurrence, which gradually progressed to assume the form of the presently visible orbital mass. Computed tomography of the orbits showed the mass extending into the left orbit causing superior displacement of the globe. After a negative locoregional and systemic metastatic screening, neoadjuvant intravenous systemic chemotherapy with cisplatin and 5‑fluorouracil were initiated in an attempt to reduce the size of the tumor. Three cycles of tri‑weekly chemotherapy resulted in a significant reduction of the orbital tumor size with the globe and the lower lid being visible, thus making a lid‑sparing orbital exenteration possible. The patient subsequently underwent an orbital exenteration and at 6‑month follow‑up, the patient was free from local and regional disease. To our knowledge, this is the first reported case where systemic neoadjuvant chemotherapy has been used to reduce the size of invasive SCC with orbital extension, thereby permitting a lid‑sparing orbital exenteration.

Epibulbar schwannoma in a 12-year-old boy: A case report and review of literature.

Schwannomas are benign, encapsulated, primary neurilemmal tumors composed of proliferating Schwann cells. Schwannomas are commonly seen in the orbit, but are rare on the epibulbar surface. Herein, we report a case of a 12‑year‑old boy who presented to us with a slow‑growing painless subconjunctival mass in the left eye. There was no intraocular extension of the mass and intra‑operatively, the mass could be clearly delineated and was excised off the underlying sclera. Histopathological examination of the mass showed typical features of schwannoma and immunohistochemistry helped to confirm the diagnosis. There was no recurrence of the lesion observed at follow‑up 26 months after surgery. Here, we describe this uncommon tumor and review the available literature. Although rare, an epibulbar schwannoma should be considered in the differential diagnosis of an amelanotic, painless subconjunctival nodular mass. Excision of the lesion is the recommended treatment.

Rhinosporidiosis of the tarsal conjunctiva.

Rhinosporidiosis is a rare infection caused by Rhinosporidium seeberi, an organism classified in its own class, mesomycetozoea. It commonly affects mucus membranes namely the nasal mucosa, pharynx and the conjunctiva. We present the case of an 8‑year‑old female who presented with a flat, red, vascular, fleshy, pedunculated mass arising from the tarsal conjunctiva of the right upper eyelid. The mass was completely excised. On histopathological examination, multiple sporangia were seen in various stages of degeneration, consistent with rhinosporidiosis. The diagnosis of rhinosporidiosis is based solely on its microscopic features, and the treatment is surgical excision. This condition is endemic in the temperate regions of the Indian subcontinent, but it has been known to occur even in the colder regions of North America and Eastern Europe. Although a rare clinical entity, the possibility of rhinosporidiosis must be borne in mind when evaluating any polypoidal conjunctival mass.

Choroidal metastases: Origin, features, and therapy.

The choroid is the most common ocular site for metastatic disease, owing to abundant vascular supply. The primary cancers that most commonly lead to choroidal metastases include breast cancer (40-47%) and lung cancer (21-29%). Bilateral, multifocal metastases are most often secondary to breast cancer, whereas unilateral, unifocal metastasis are more commonly found with lung cancer. The treatment of choroidal metastasis depends on the systemic status of the patient and number, location, and laterality of the choroidal tumors. Treatment options include observation in patients with poor systemic status or those with resolved or asymptomatic disease; systemic chemotherapy, immunotherapy, hormone therapy, or whole eye radiotherapy if the metastases are active, multifocal and bilateral; plaque radiotherapy, transpupillary radiotherapy, or photodynamic therapy for active, solitary metastasis; and enucleation for those with blind painful eye. A database search was performed on PubMed, using the terms “choroidal metastasis,” or “choroidal metastases,” in combination with terms such as “treatment,” “features,” or “diagnosis.” Relevant articles were extracted and reviewed.