Atlantic Coast Retina Club 2023: Attending Cases 6

Saghar Bagheri, MD, PhD
Massachusetts Eye and Ear
Boston, MA

Session C of the second day of the Atlantic Coast Retinal Club Meeting on February 3, 2023, was moderated by Drs. Ivana Kim and Carol Shields.

Dr. David H. Abramson from Memorial Sloan Kettering Cancer Center presented a case of a 7-month-old boy who presented with two weeks of eye redness and an abnormal pupil reflex, as well as the eye “wandering out” with no history of trauma, no medical history and no family history of retinoblastoma or any other eye conditions. On exam, the eye looked quiet and had no light perception with a relative afferent pupillary defect. The cornea was clear, the anterior chamber was deep and quiet, the IOP was normal, the lens was displaced nasally, the fundus appeared abnormal with a question of a dark mass and retinal details and the optic nerve were not visible. The fellow eye was normal. B-scan and a UBM showed a mass extending from the retina very far anteriorly to the ciliary body. MRI of the orbits was performed and T1 weighted images were consistent with an intraocular mass containing hemorrhage or melanin. A biopsy of the mass was obtained, and the pathology results were concerning for melanoma but also revealed melanocytoma-like cells. 10 days later, an enucleation of this eye was performed, and histopathology showed a mixture of melanoma and melanocytoma-like cells, and BAP-1 was normal. Latest follow up of four years has the patient alive and well. Carol Shields commented that melanocytomas can be giant. Dr. Abramson summarized that melanomas in young children are extremely rare and cited a paper by Shields describing that <1% of patients with uveal melanoma are younger than the age of 21 years. He also added that there are only 7 cases of congenital uveal melanoma reported in the literature. Finally, he suggested to name the diagnosis “endopapillary uveal melanocytic tumor of childhood”.

Dr. Drew H. Scoles from Children’s Hospital of Philadelphia presented a case of a newborn who on prenatal ultrasound was found to have microcephaly, absent corpus callosum, cavum septum pellucidum, and ventriculomegaly, and was born at a gestational age of 39 weeks (3kg) with Apgar scores of 3, 6 and 7 and then intubated at birth and initially on palliative care. Ophthalmology was consulted at 1 week of life to rule out TORCH-related disease. The work up showed maternal CMV titers positive for IgG and IgM, but avidity testing argued against acute infection. On exam, there was no appreciable response to bright light in either eye. The anterior segment showed a normal iris and lens and no posterior plaque but a dense stalk that appeared to be perfused in both eyes. There was a large pre-retinal hemorrhage in the right eye and poor vascularization. The left eye had a similar stalk and poor vascularization, as well as the so-called double ring sign and there was no nerve tissue but just a hole. The FA of both eyes was not concerning for neovascularization, however, showed staining of the stalk and diffuse staining at the vascular and avascular border. At this point, laser was performed given concerns for possible complications due to future neovascularization and tractional detachment. Genetic testing revealed a TUBA1A mutation and the diagnosis of bilateral persistent fetal vasculature and optic nerve hypoplasia due to TUBA1A tubulinopathy was made. Dr. Scoles stated that so far there have been no associations between TUBA1A mutations and optic nerve hypoplasia, as well as none with persistent fetal vasculature in the literature.

Dr. Deeba Husain from Mass. Eye and Ear presented a case of a 33-year-old female who presented with worse vision in the left eye after giving birth of her first child four months prior. Her past ocular history was unclear, however, she thought that her vision in the left eye has been worse than the right eye for a long time and reported a visual field defect in the left eye based on which she was diagnosed with glaucoma in 2019 but never treated for it. She was also told that her glasses prescription was different between both eyes although she was currently not wearing any glasses. She had no past medical history, and her review of systems was completely negative. On exam, VA 20/20 OD and 20/200 OS, pupils, IOP and anterior segment were normal OU. The right fundus appeared normal and the left fundus revealed some RPE changes in the temporal macula, as well as some pigmentary changes in the midperiphery. A fundus autofluorescence was obtained and showed a radial pattern of hyperfluorescence extending from the nerves to the periphery in both eyes, as well as some mottled hyper- and hypofluorescence in the macula of the left eye corresponding to the RPE changes seen on fundus exam. The OCT showed some irregularity of the outer retina in the right eye and central outer retinal atrophy in the left eye. Fluorescein angiography showed peripheral vascular leakage in both eyes, as well as a window defect in the macula of the left eye corresponding to the area of atrophy. Infectious and inflammatory causes, and IRDs were high on the differential. Lab work was obtained for infectious and inflammatory causes, and all came back negative. Full-field ERG was obtained and showed reduced rod and cone responses more in the left than the right eye. Following this, genetic testing was performed and showed a pathogenic variant in the RP2 gene. Per Dr. Husain, gene mutations in the RP2 gene lead to X-linked recessive retinitis pigmentosa and therefore, the patient was diagnosed to be a manifesting carrier for X-linked retinitis pigmentosa 2. Dr. Husain summarized that female carriers of RP have been described in the literature to have this specific radial pattern of hyperfluorescence that was also seen in her case.

Dr. Noel Horgan from Royal Victoria Eye and Ear Hospital in Dublin presented a case of an 83-year-old Caucasian man who was referred by Neurology in August 2022. His past medical history included prostate surgery for a benign lesion. He had undergone cataract surgery in November 2017 in his right eye and in December 2017 in his left eye, however, noticed only little improvement in his vision post-operatively. His ophthalmologist obtained an ERG which showed an electronegative response on dark adapted ERG and thought that this test result was suggestive of cancer associated retinopathy, leading to referral to Neuro-Ophthalmology and Neurology. The patient underwent a systemic work up that did not reveal a systemic malignancy and anti-retinal antibodies including anti-recoverin, anti-enolase, and transducing alpha were all negative. Other serology that included a VDRL, phytanate, as well as anti-MOG and aquaporin antibodies were all negative as well. The patient continued to have a slow gradual decline in vision (OD > OS) and was treated with IVIG for possible underlying CAR for 5 days each month for 4 consecutive months followed by quarterly treatment. Dr. Horgan stated that the patient was referred to him about two years after initiation of the patient’s first treatment which was about 5 years after the patient’s cataract surgery. His VA at that time was HM OD and 20/50 OS. His pupils and IOP were normal and there was no intraocular inflammation in both eyes. A repeat ERG was performed which was “essentially unchanged” to the patient’s initial ERG. Fundus exam revealed attenuation of the retinal vasculature and a “thinned” retina in both eyes. Fundus autofluorescence showed an area of hypofluorescence in the central macula in the right eye and some mottled hypofluorescence in the central macula of the left eye. OCT showed diffuse atrophy of the outer retina in both eyes. Dr. Horgan then asked the audience if this case could be consistent with CAR, MAR or autoimmune retinopathy, or if this is dry AMD, and if IVIG treatment should be continued. When asked about genetic testing, Dr. Horgan stated that it has not been performed yet. He then asked the audience if anyone has seen cases of CAR or MAR in which the cancer has not surfaced for so many years, and Dr. Jose Pulido answered “absolutely”. One speaker in the audience did not think that this could be a case of dry AMD given the ERG changes. Finally, Dr. Pulido commented that he thinks this is a case of an IRD and recommended obtaining genetic testing.

Last in this session, Dr. Amani Fawzi from Northwestern University presented a case of a 29-year-old female with a 15-year history of headaches associated with bilateral optic nerve head swelling and massive peripapillary exudation and associated structural and vascular changes. Her VA was 20/20 OD and 20/150 OS. The patient underwent several lumbar punctures given the suspicion for IIH, however, all work up was negative. 3 years later, she presented to Dr. Fawzi and her VA OD was stable at 20/20 but she was now LP in the left eye due to a total exudative retinal detachment. Despite the VA of 20/20 in the right eye, the fundus exam showed a peripapillary mass lesion that was encroaching the fovea and the patient had also started to become symptomatic in the right eye. At this point, VHL was high on the differential. OCT of the right eye showed a peripapillary mass lesion as well as intra- and subretinal fluid. Fluorescein angiography showed well defined borders of the peripapillary lesion as well as telangiectasia and leakage in the right eye. There was a high suspicion for HIF-2 paraganglioma-somatostatinoma-polycythemia syndrome, although the differential diagnosis also included retinal capillary hemangiomas (VHL) and retinal vasoproliferative tumors (aka reactive retinal astrocytic tumor, RRAT). The patient’s past medical and family history, as well as genetic testing for VHL and HIF2 was negative. Eventually, Dr. Fawzi decided to perform a diagnostic enucleation of the patient’s left eye and the pathology report was concerning for a reactive retinal astrocytic tumor. Genotyping of the optic tumor did not reveal a somatic HIF2 mutation. Given a decrease of the patient’s VA from 20/20 to 20/200 in the right eye due to lesion progression and subretinal fluid into the macula, monthly to bi-weekly anti-VEGF injections in addition to bi-monthly dexamethasone intravitreal implants were administered but with minimal effect. Dr. Jasmine Frances commented that there is a drug that is a HIF-inhibitor called belzutifan and added that although in this patient no somatic HIF mutation was identified, there still could be an abnormality in this pathway and it would be worth trying this medication. Dr. Fawzi answered that this drug was not available to her at the time she saw this patient. Dr. Carol Shields added that belzutifan is now available for the treatment of CNS hemangioblastoma and renal cell carcinoma and secondarily can cause VHL tumors in the eye to resolve although this drug is not approved for the only treatment of the eye. Dr. Jasmine Frances added that this drug cannot be given in pregnancy and therefore, would have to be given to this patient with caution. Dr. Shields suggested to investigate if the patient has an mTOR mutation. Dr. Fawzi concluded that she made the decision to do peripapillary PDT for this patient’s right eye over three sessions which led to a regression of the lesion. The patient received a few more anti-VEGF injections and now five years later has a VA of 20/150 in the right eye. The final diagnosis was presumed HIF2-related bilateral peripapillary reactive astrocytic lesions without identified somatic mutations in the lesion.