Elham Sadeghi MD
University of Pittsburgh (UPMC), Pittsburgh, PA
Retinoblastoma case
David H. Abramson MD
Dr. David Abramson presented the case of a 1.5-year-old girl with untreated bilateral retinoblastoma. The right eye had no light perception and was notable for a cloudy cornea, rubeosis, elevated intraocular pressure, total retinal detachment, and an extinguished ERG, with MRI showing no optic nerve involvement. Plasma cell-free DNA (cfDNA) testing disclosed levels of 5.82% for RB1 and 0.62% for BCOR. He performed right eye enucleation, and pathology demonstrated massive choroidal invasion with ciliary body involvement. Remarkably, intraoperative cfDNA levels dropped by 95% within 40 minutes of optic nerve transection, and repeat testing was negative, leading to the decision to forgo systemic chemotherapy. The fellow eye also initially had no light perception, total retinal detachment, extinguished ERG, and extensive tumor on ultrasound. While management options included enucleation, external beam radiation, or systemic chemotherapy, Dr. Abramson opted for intra-arterial chemotherapy with melphalan, topotecan, and carboplatin. At 4.5 years of follow-up, the patient remains free of metastasis despite the initial massive choroidal invasion and absence of systemic chemotherapy and has achieved a visual acuity of 20/50 in the treated eye.
A choroidal mass with retinal invasion
Ayman Elnahry, MD, PhD
Dr. Ayman Elnahry presented the case of a 52-year-old man with an amelanotic choroidal lesion in the left eye that had been present for over a year. The lesion was initially suspected to represent choroidal metastasis; however, an extensive systemic workup was negative. The differential diagnosis included choroidal melanoma versus a granulomatous lesion. The patient was treated with sub-Tenon Kenalog, oral corticosteroids, and an Ozurdex implant, but showed minimal response, and treatment was complicated by cataract progression. An inflammatory workup was also unrevealing. On examination, visualization was hazy, disclosing a 13 × 7 mm temporal amelanotic choroidal mass with a 4 × 4 mm area of overlying retinal invasion, extending subfoveally and approaching the optic nerve. The lesion was centered at the 3 o’clock position and was associated with subretinal fluid, surrounding RPE changes, and additional peripheral RPE alterations with pigmentation. OCT demonstrated a choroidal mass with both intraretinal and subretinal fluid. MRI showed no orbital extension or optic nerve involvement. Fine-needle aspiration biopsy revealed a PRAME-negative, class 1A profile with a low discriminant value of 0.48, and genetic testing was positive for GNAQ and EIF1AX mutations. The final diagnosis was amelanotic choroidal melanoma with low metastatic risk, and enucleation was performed.
Mystery case
Jasmine H. Francis, MD, FACS
Dr. Francis presented the case of a 70-year-old woman who complained of blurry vision (OD), with a VA of 20/125. FAF demonstrated hyperautofluorescence in the macula, while OCT revealed choroidal infiltration with secondary retinal fluid. Ultrasound confirmed diffuse choroidal thickening. The patient had multiple medical comorbidities and was taking several medications, including amlodipine, apixaban, dulaglutide, dexlansoprazole, empagliflozin, irbesartan, and rosuvastatin. Given concern for an amelanotic melanoma and its differential diagnoses, a PET scan was obtained and showed widespread lymphadenopathy; however, biopsy of an axillary lymph node demonstrated benign lymphoid hyperplasia. At six-week follow-up, her visual acuity and clinical findings remained stable, and Dr. Francis elected not to pursue radiation, steroid therapy, or rituximab. Instead, dulaglutide was discontinued as a potential contributor to the choroidal findings. Remarkably, within 10 days, the choroidal thickening completely resolved. Dr. Francis also described a similar case involving a 47-year-old diabetic patient with blurred vision in the left eye. This patient showed partial response to oral steroids and a sub-Tenon Kenalog injection but experienced recurrence after 14 months. Following discontinuation of dulaglutide due to gastritis, OCT findings resolved, VA returned to 20/20, and no recurrence was observed. The key takeaway is that dulaglutide, the only GLP-1 receptor agonist containing polysorbate 80, may provoke inflammatory ocular changes, though its role remains incompletely understood, particularly as tirzepatide also contains this excipient.
Mystery case
Lisa Koenig, MD
Dr. Koenig presented the case of a man in his 70s who reported bilateral blurry vision. He had a history of diabetes and was undergoing routine eye examinations, which were initially unremarkable. VA was 20/20 in both eyes. Color fundus photography revealed yellow subretinal deposits with corresponding hyperautofluorescence in both eyes, involving the left macula. OCT of the right eye demonstrated subretinal deposits, while the left eye showed both subretinal fluid and deposits. The patient had a prior history of cutaneous melanoma and a pancreatic tumor, raising concern for a paraneoplastic or metastatic process. However, plasma cfDNA testing showed a single NF1 mutation with low variant allele frequency, and PET imaging was unremarkable. Full-field ERG was normal, while multifocal ERG showed central depression corresponding to the area of subretinal fluid. At six-month follow-up, there were no changes in examination or imaging findings. EOG demonstrated absent light rise in both eyes with a reduced Arden ratio below 1.5. Genetic testing was sent and was pending at the time of presentation. Dr. Koenig suggested that if genetic testing is negative, the most likely diagnosis would be pachyvitelliform maculopathy, representing an acquired vitelliform lesion within the pachychoroid spectrum disease.
Eye of the tiger
Sara Lally, MD
Dr. Lally presented the case of a 58-year-old woman with a history of stage IV metastatic cutaneous melanoma that was BRAF positive. She was initially treated with Tafinlar and Mekinist, with marked improvement of all systemic metastases within two months. Therapy was discontinued because of neuropathy, and treatment was transitioned to nivolumab. Three months later, she presented with blurred vision in the left eye, her better-seeing eye, with a VA of 20/50 and vitreous debris. OCT demonstrated a sheet of hyperreflective cells overlying the retinal layers, and ultrasound confirmed debris within the vitreous cavity. Vitreous biopsy revealed vitreous metastasis from cutaneous melanoma. She underwent three intravitreal melphalan injections administered at the 12 o’clock position. Subsequently, she developed an amelanotic conjunctival nodule nasally, suspicious of metastatic disease, which was excised and treated with brachytherapy. Despite continued intravitreal therapy, vitreous biopsy showed rare, atypical cells concerning persistent or recurrent melanoma, prompting five additional melphalan injections. She developed radiation-induced cataract and underwent cataract extraction after repeat biopsy showed no malignant cells. Postoperatively, she developed choroidal effusions requiring pars plana vitrectomy with gas tamponade; pathology revealed only hemorrhage. Months later, she developed massive subretinal hemorrhage with vision declining to light perception, along with brown cells in the anterior chamber. Repeat biopsy confirmed metastatic melanoma in the aqueous and subretinal space. Treatment options included further intravitreal chemotherapy, enucleation, radiotherapy, or intra-arterial chemotherapy, and she elected to undergo intra-arterial chemotherapy, as it was her better seeing eye. After four treatment sessions, the intraocular disease was successfully controlled.
