ACRC/Macula 2025 – Mystery Cases 7, 8, 9

Luis Acaba-Berrocal, MD
Martin Calotti, MD
Sidra Zafar, MD
Wills Eye Hospital

SESSION 7

The afternoon continued with Session 7, moderated by Dr. Jay Chhablani and Dr. Demetrios Vavvas. The session began with a case of Perifoveal Anomalous Vascular Complex (PEVAC) with subretinal fluid presented by Dr. Elham Sadeghi, a research fellow from the University of Pittsburgh School of Medicine. Although the lesion was adjacent to the foveal center, it was successfully treated with focal eye-tracking laser, resulting in the resolution of subretinal fluid. Dr. Chhablani emphasized the importance of using lasers for PEVAC lesions, while Dr. Freund highlighted the need for low power and long duration to avoid damaging the outer retina/RPE.

Dr. Sidra Zafar, a vitreoretinal fellow from Wills Eye Hospital, presented an atypical case of bilateral primary vitreoretinal lymphoma initially misdiagnosed as viral retinitis. The patient had negative vitreous biopsies in both eyes and was MYD88-negative. The diagnosis was ultimately confirmed through a retinal biopsy, which revealed pathology consistent with diffuse large B-cell lymphoma. The patient was treated with intravitreal methotrexate, leading to improvement. Dr. Zafar also shared the surgical video of the biopsy.

Next, Dr. Saeed Mohammadi, a fellow from Northwestern University, presented a case involving a teenage patient with enhanced S-cone syndrome and CME. ERG showed an exaggerated S-cone response and the diagnosis was confirmed with genetic testing, which identified an NR2E3 mutation. The CME was successfully managed with topical dorzolamide. Dr. Pulido commented on the importance of examining the parents of such patients in clinic as well.

Following this, Dr. Bani Antonio-Aguirre, a research fellow at Duke University, presented a case of a toddler with exudative vitreoretinopathy, neovascularization, and total retinal detachment. The patient also had congenital delays and heart defects. After ruling out infectious and inflammatory causes and finding negative initial genetic tests for FEVR, incontinentia pigmenti, and sickle cell disease, whole exome sequencing revealed an EPH A4 de novo mutation. This mutation, involved in embryogenesis and neovascular suppression, had not been previously described. The patient was treated with PRP and anti-VEGF injections. Dr. Yonekawa stressed that laser therapy should be the primary management to stabilize the eye in these types of eyes.

The session concluded with Dr. Aruba Zafar, an ocular oncology fellow from Wills Eye Hospital, presenting a case of phakomatosis pigmentovascularis. The patient exhibited bilateral nevus flammeus, diffuse scleral and iris melanocytosis, and choroidal hyperpigmentation. Genetic testing revealed a GNA11 mutation. Dr. Zafar emphasized the importance of a multidisciplinary approach, as these patients are at risk for glaucoma, choroidal hemangioma, and CNS lesions.

SESSION 8

The eighth session was moderated by Dr. John Miller, and Dr. Stephen Tsang. Dr. Bita Momenaei from Wills Eye Hospital first presented a case of an African American boy with nystagmus and progressive visual decline in both eyes. OCT demonstrated mild grade 1 foveal hypoplasia, prompting genetic testing, which revealed a homozygous point mutation in the OCA2 gene, leading to a diagnosis of type 2 oculocutaneous albinism. Dr. Momenaei emphasized the importance of realizing that oculocutaneous albinism occurs in 1% of patients with Prader-Willi or Angelman Syndrome.

Next, Dr. M. Ludovica Ruggeri from Wilmer Eye Institute presented a case of a woman in her 30s with a past ocular history of bilateral optic atrophy who presented for evaluation of decreased visual acuity in both eyes since childhood. She was noted to have a family history of progressive vision loss in multiple family members. OCT demonstrated a “fuzzy” disruption of the EZ line in both eyes. While microperimetry was unremarkable, full-field ERG revealed moderate generalized cone dysfunction. Dr. Ruggeri emphasized the importance of utilizing a multifocal ERG in this case which revealed foveal suppression, in both eyes. The patient subsequently underwent genetic testing and was diagnosed with RP1L1 related occult macular dystrophy.

Dr. Edward (Ned) Lu from Mass Eye & Ear then shared a unique case of a man of Eastern European Jewish descent, and a past ocular history of a “form of macular degeneration” who was evaluated for a one year history of bilateral decreased vision. He also reported intermittent myalgias. He was found to have granular pigmentary changes and drusenoid macular deposits in both eyes. On OCT, he was noted to have RPE elevations, and focal areas of EZ line disruptions. FA demonstrated hyperautofluorescence within the macular. Interestingly, full-field ERG, multifocal ERG, and genetic testing were unrevealing. The patient returned nine years later, with progressive vision decline. There appeared to be decreased paracentral sensitivity on microperimetry, and repeat genetic testing was notable for CCTG repeat expansion, securing a diagnosis of macular dystrophy associated with myotonic dystrophy, type 2.

Dr. Y. Stephanie Zhang also from Mass Eye & Ear concluded the session with a case of an older man presenting with a one-month history of floaters, blurry vision, and sensitivity to light, in the right eye. Past medical history was notable for psoriatic arthritis being managed with a JAK inhibitor. He was found to have vitreous cell, 360-degree non-perfusion, and retinal whitening in the periphery. Aqueous PCR was positive for CMV, which was treated accordingly. After discussion with his rheumatologist, the JAK inhibitor was discontinued. However, three weeks later, his symptoms recurred, as did his degree of non-perfusion. OCT also showed peri-foveal PAMM-like lesions. The patient was ultimately diagnosed with CMV retinal necrosis with pan-retinal occlusive vasculopathy.

SESSION 9

The ninth and final session Uveitis and Genetics was moderated by Dr. Andre Witkin and Dr. Lee Jampol.

Dr. Omar Halawa from Wilmer first presented a complex case of teenage boy who presented with diffuse cotton wool spots and scattered intraretinal hemorrhages in both eyes associated with arthralgias and skin rash. Fluorescein angiography showed perivascular leakage with peripheral non-perfusion. The patient was diagnosed with bilateral occlusive vasculitis secondary to systemic lupus erythematous prompting inpatient admission for treatment with IV steroids. He was also started on hydroxychloroquine and mycophenolate mofetil. Despite medical treatment, the patient developed worsening non-perfusion neccesiting treatment with PRP and rituximab infusions. He was also started on anticoagulation. His clinical course was later complicated by a non-clearing vitreous hemorrhage for which a PPV was done. On his last follow-up visit, the patient’s visual acuity had improved, and his disease course had stablized.

Dr. Whitney Sambhariya, also from Wilmer, then showed a case of a middle aged woman with acute onset of left eye exudative subretinal fluid. The patient had a history of right eye ciliochoroidal melanoma status post plaque brachytherapy. She was found to have lung metastasis and was treated with nivolumab and ipilimumab infusions prior to switching to tebentafusp in 2022. The patient’s tebentafusp was eventually stopped due to grade 1 cytokine release syndrome but 1 month following cessation of the infusion, she developed blurred vision in her left eye. The patient was diagnosed with tebentafusp-associated retinopathy. At her 6-week follow-up, the subretinal fluid appeared stable and her visual acuity had improved.

Dr. Loka Thangamathesvaran discussed complex management for a Candida endophthalmitis case in a woman 12 weeks following cataract surgery. Initial treatment consisted of intravitreal and systemic voriconazole with some improvement but eventually required vitrectomy for dense persistent vitritis. The IOL was not removed. Three days following the vitrectomy, the patient developed a deep choroidal lesion that eventually resolved with systemic anti-fungal treatment. The oral antifungal was stopped after a 3-month course but within a week of stopping treatment, the patient developed new retinal deposits. Oral fluconazole was restarted, and the patient has been doing well with no new lesions.

Ari August, one of the award winners, presented a case of man who had presented for an annual eye examination. OCT retina of the right eye showed subtle loss of inner retinal laminations, pinpoint hyper-reflective foci at the fovea and irregular reflectivity of the IS/OS junction. Similar findings were noted in the left eye OCT. Fundus autofluorescence showed stippled hyper and hypofluorescence. The patient was also noted to have dermatologic findings and upon further history, also reported pulmonary and renal issues. The patient was diagnosed with the rare condition of Birt-Hogg-Dube syndrome.